Discovery and Optimization of Macrocyclic Quinoxaline-pyrrolo-dihydropiperidinones as Potent Pim-1/2 Kinase Inhibitors.

abstract：:In light of the biomedical significance of metallo-β-lactamases (MβLs), ten new mercaptoacetic acid thioester amino acid derivatives were synthesized and characterized. Biological activity assays indicated that all these synthesized compounds are very potent inhibitors of L1, exhibiting an IC50 value range of 0.018-2....

journal_title：ACS medicinal chemistry letters

authors： Liu XL,Shi Y,Kang JS,Oelschlaeger P,Yang KW

更新日期：2015-04-23 00:00:00

abstract：:A new prosthetic group referred to as the triazole appending agent (TAAG) was developed as a means to prepare targeted radioiodine-based molecular imaging and therapy agents. Tributyltin-TAAG and the fluorous analogue were synthesized in high yield using simple click chemistry and the products labeled in greater than ...

journal_title：ACS medicinal chemistry letters

authors： Darwish A,Blacker M,Janzen N,Rathmann SM,Czorny S,Hillier SM,Joyal JL,Babich JW,Valliant JF

更新日期：2012-02-18 00:00:00

abstract：:In this paper, we describe the discovery and optimization of a series of noncovalent reversible epidermal growth factor receptor inhibitors of EGFRL858R/T790M/C797S. One of the most promising compounds, 25g, inhibited the enzymatic activity of EGFRL858R/T790M/C797S with an IC50 value of 2.2 nM. Cell proliferation assa...

journal_title：ACS medicinal chemistry letters

authors： Li Q,Zhang T,Li S,Tong L,Li J,Su Z,Feng F,Sun D,Tong Y,Wang X,Zhao Z,Zhu L,Ding J,Li H,Xie H,Xu Y

更新日期：2019-05-22 00:00:00

abstract：:We have synthesized several C7-spirocyclic analogues of vorapaxar and evaluated their in vitro activities against PAR-1 receptor. Some of these analogues showed activities and rat plasma levels comparable to vorapaxar. Compound 5c from this series showed excellent PAR-1 activity (K i = 5.1 nM). We also present a model...

journal_title：ACS medicinal chemistry letters

authors： Chelliah MV,Eagen K,Guo Z,Chackalamannil S,Xia Y,Tsai H,Greenlee WJ,Ahn HS,Kurowski S,Boykow G,Hsieh Y,Chintala M

更新日期：2014-03-11 00:00:00

abstract：:A series of fluorine-substituted monomeric and dimeric cRGD peptide derivatives, such as cRGD-ADIBOT-F (ADIBOT = azadibenzocyclooctatriazole), di-cRGD-ADIBOT-F, cRGD-PEG5-ADIBOT-F, and di-cRGD-PEG5-ADIBOT-F, were prepared by strain-promoted alkyne azide cycloaddition (SPAAC) reaction of the corresponding aza-dibenzocy...

journal_title：ACS medicinal chemistry letters

authors： Kim HL,Sachin K,Jeong HJ,Choi W,Lee HS,Kim DW

更新日期：2015-02-06 00:00:00

abstract：:We recently reported a series of 2,6-dipeptidyl-anthraquinone conjugates (AQs) as Trans-Activation Response element (TAR) RNA-binding agents able to inhibit in vitro the HIV-1 nucleocapsid (NC) protein-mediated processes. Because NC is a highly adaptable nucleic acid chaperone assisting several crucial steps along rev...

journal_title：ACS medicinal chemistry letters

authors： Gamba E,Sosic A,Saccone I,Magli E,Frecentese F,Gatto B

更新日期：2020-03-23 00:00:00

abstract：:Inhibition of phosphoinositide 3-kinase (PI3K) signaling is an appealing approach to treat brain tumors, especially glioblastoma multiforme (GBM). We previously disclosed our successful approach to prospectively design potent and blood-brain barrier (BBB) penetrating PI3K inhibitors. The previously disclosed molecules...

journal_title：ACS medicinal chemistry letters

authors： Heffron TP,Ndubaku CO,Salphati L,Alicke B,Cheong J,Drobnick J,Edgar K,Gould SE,Lee LB,Lesnick JD,Lewis C,Nonomiya J,Pang J,Plise EG,Sideris S,Wallin J,Wang L,Zhang X,Olivero AG

更新日期：2016-02-16 00:00:00

abstract：:A series of 3-deoxy-3-N-arylated-β-d-galactoside and -guloside derivatives have been synthesized by cesium fluoride/trimetylsilylaryl triflate-mediated benzyne generation and N-arylation of 3-deoxy-3-amino-β-d-galactosides and -gulosides, respectively. Evaluation as ligands to galectin-1, 2, 3, 4N (N-terminal domain),...

journal_title：ACS medicinal chemistry letters

authors： Mahanti M,Pal KB,Sundin AP,Leffler H,Nilsson UJ

更新日期：2019-12-04 00:00:00

abstract：:Reactive oxygen species, contributing to oxidant-antioxidant imbalance, initiate damage to the airways cells, inflammatory processes, and further pathophysiological effects. Enhancing antioxidant properties is the main prophylactic and therapeutic challenge. In this work, a newly synthesized and biocompatible structur...

journal_title：ACS medicinal chemistry letters

authors： Wiśniewski M,Bieniek A,Roszek K,Czarnecka J,Bolibok P,Ferrer P,da Silva I,Terzyk AP

更新日期：2018-11-19 00:00:00

abstract：:This study was aimed at investigating the antitumor activity of novel 2-oxindole derivatives against a well-characterized human nonsmall cell lung cancer (NSCLC) cell line. Test compounds produced an antiproliferative activity in the low micromolar/submicromolar range of concentrations and significantly induced typica...

journal_title：ACS medicinal chemistry letters

authors： Nesi G,Sestito S,Mey V,Ricciardi S,Falasca M,Danesi R,Lapucci A,Breschi MC,Fogli S,Rapposelli S

更新日期：2013-10-18 00:00:00

abstract：:Purine-rich foods have long been suspected as a major cause of hyperuricemia. We hypothesized that inhibition of human concentrative nucleoside transporter 2 (hCNT2) would suppress increases in serum urate levels derived from dietary purines. To test this hypothesis, the development of potent hCNT2 inhibitors was requ...

journal_title：ACS medicinal chemistry letters

authors： Tatani K,Hiratochi M,Nonaka Y,Isaji M,Shuto S

更新日期：2015-01-28 00:00:00

abstract：:The first allosteric, type III inhibitor of LIM-kinase 2 (LIMK2) is reported. A series of molecules that feature both an N-phenylsulfonamide and tertiary amide were not only very potent at LIMK2 but also were extremely selective against a panel of other kinases. Enzymatic kinetic studies showed these molecules to be n...

journal_title：ACS medicinal chemistry letters

authors： Goodwin NC,Cianchetta G,Burgoon HA,Healy J,Mabon R,Strobel ED,Allen J,Wang S,Hamman BD,Rawlins DB

更新日期：2014-08-07 00:00:00

abstract：:All eight of the major active metabolites of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221, compound 1), an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 that has entered the clinic for the treatment of type 2 diabetes, were synthetically prepared and confirmed...

journal_title：ACS medicinal chemistry letters

authors： Li A,Yuan CC,Chow D,Chen M,Emery MG,Hale C,Zhang X,Subramanian R,St Jean DJ Jr,Komorowski R,Véniant M,Wang M,Fotsch C

更新日期：2011-09-13 00:00:00

abstract：:Compound libraries provide a starting point for multiple biological investigations, but the structural integrity of compounds is rarely assessed experimentally until a late stage in the research process. Here, we describe the discovery of a neuroprotective small molecule that was originally incorrectly annotated with ...

journal_title：ACS medicinal chemistry letters

authors： Kaplan A,Stockwell BR

更新日期：2015-07-29 00:00:00

abstract：:Glucocorticoids are one of the most utilized and effective therapies in treating T-cell acute lymphoblastic leukemia. However, patients often develop resistance to glucocorticoids, rendering these therapies ineffective. We screened 9517 compounds, selected for their lead-like properties, chosen from among 3 372 615 co...

journal_title：ACS medicinal chemistry letters

authors： Cantley AM,Welsch M,Ambesi-Impiombato A,Sanchez-Martin M,Kim MY,Bauer A,Ferrando A,Stockwell BR

更新日期：2014-04-25 00:00:00

abstract：:The multistep preparation of (11)C-levetiracetam ((11)C-LEV) was carried out by a one-pot radiosynthesis with 8.3 ± 1.6% (n = 8) radiochemical yield in 50 ± 5.0 min. Briefly, the propionaldehyde was converted to propan-1-imine in situ as labeling precursor by incubation with ammonia. Without further separation, the im...

journal_title：ACS medicinal chemistry letters

authors： Cai H,Mangner TJ,Muzik O,Wang MW,Chugani DC,Chugani HT

更新日期：2014-08-19 00:00:00

abstract：:The retinoic acid receptor-related orphan nuclear receptor γt (RORγt), a promising therapeutic target, is a major transcription factor of genes related to psoriasis pathogenesis such as interleukin (IL)-17A, IL-22, and IL-23R. On the basis of the X-ray cocrystal structure of RORγt with 1a, an analogue of the known pip...

journal_title：ACS medicinal chemistry letters

authors： Nakajima R,Oono H,Sugiyama S,Matsueda Y,Ida T,Kakuda S,Hirata J,Baba A,Makino A,Matsuyama R,White RD,Wurz RΡ,Shin Y,Min X,Guzman-Perez A,Wang Z,Symons A,Singh SK,Mothe SR,Belyakov S,Chakrabarti A,Shuto S

更新日期：2020-02-27 00:00:00

abstract：:Water-soluble cyclodextrin (CyD) complexed with porphyrin derivatives with different substituents in the meso-positions showed different photodynamic activities toward cancer cells under illumination at wavelengths over 600 nm, the most suitable wavelengths for photodynamic therapy (PDT). In particular, aniline- and p...

journal_title：ACS medicinal chemistry letters

authors： Ikeda A,Satake S,Mae T,Ueda M,Sugikawa K,Shigeto H,Funabashi H,Kuroda A

更新日期：2017-04-19 00:00:00

abstract：:A series of 12N-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N'-end could greatly enhance antiproliferation potency. Among them,...

journal_title：ACS medicinal chemistry letters

authors： Bi C,Zhang N,Yang P,Ye C,Wang Y,Fan T,Shao R,Deng H,Song D

更新日期：2017-01-05 00:00:00

abstract：:Modifications at the basic nitrogen of the benzomorphan scaffold allowed the development of compounds able to segregate physiological responses downstream of the receptor signaling, opening new possibilities in opioid drug development. Alkylation of the phenyl ring in the N-substituent of the MOR-agonist/DOR-antagonis...

journal_title：ACS medicinal chemistry letters

authors： Pasquinucci L,Parenti C,Ruiz-Cantero MC,Georgoussi Z,Pallaki P,Cobos EJ,Amata E,Marrazzo A,Prezzavento O,Arena E,Dichiara M,Salerno L,Turnaturi R

更新日期：2020-01-28 00:00:00

abstract：:Two novel benzofuran derivatives coupled with (99m)Tc complexes were tested as probes for imaging cerebral β-amyloid plaques using single photon emission tomography. Although both derivatives bound to Aβ(1-42) aggregates, (99m)Tc-BAT-BF showed higher affinity than (99m)Tc-MAMA-BF. In sections of brain tissue from an a...

journal_title：ACS medicinal chemistry letters

authors： Ono M,Fuchi Y,Fuchigami T,Kobashi N,Kimura H,Haratake M,Saji H,Nakayama M

更新日期：2010-08-02 00:00:00

abstract：:Bacterial RNA polymerase (RNAP) is essential for transcription and is an antibacterial target for small molecule inhibitors. The binding region of myxopyronin B (MyxB), a bacterial RNAP inhibitor, offers the possibility of new inhibitor design. The molecular design program SPROUT has been used in conjunction with the ...

journal_title：ACS medicinal chemistry letters

authors： McPhillie MJ,Trowbridge R,Mariner KR,O'Neill AJ,Johnson AP,Chopra I,Fishwick CW

更新日期：2011-07-29 00:00:00

abstract：:Bone Morphogenetic Protein 1 (BMP1) inhibition is a potential method for treating fibrosis because BMP1, a member of the zinc metalloprotease family, is required to convert pro-collagen to collagen. A novel class of reverse hydroxamate BMP1 inhibitors was discovered, and cocrystal structures with BMP1 were obtained. T...

journal_title：ACS medicinal chemistry letters

authors： Kallander LS,Washburn D,Hilfiker MA,Eidam HS,Lawhorn BG,Prendergast J,Fox R,Dowdell S,Manns S,Hoang T,Zhao S,Ye G,Hammond M,Holt DA,Roethke T,Hong X,Reid RA,Gampe R,Zhang H,Diaz E,Rendina AR,Quinn AM,Willette

更新日期：2018-07-02 00:00:00

abstract：:A number of biologically active nucleoside analogues contain the adenine isostere 4-amino-pyrrolo[2,1-f][1,2,4]triazine connected to various sugar moieties through a C-C anomeric linkage. We employed palladium-catalyzed cross-coupling chemistry to promptly functionalize the 7-position of such a heterocyclic scaffold w...

journal_title：ACS medicinal chemistry letters

authors： Li Q,Groaz E,Persoons L,Daelemans D,Herdewijn P

更新日期：2020-07-09 00:00:00

abstract：:Myeloperoxidase (MPO) is a key antimicrobial enzyme, playing a normal role in host defense, but also contributing to inflammatory conditions including neuroinflammatory diseases such as Parkinson's and Alzheimer's. We synthesized and characterized more than 50 quinazolin-4(1H)-one derivatives and showed that this clas...

journal_title：ACS medicinal chemistry letters

authors： Li Y,Ganesh T,Diebold BA,Zhu Y,McCoy JW,Smith SM,Sun A,Lambeth JD

更新日期：2015-08-31 00:00:00

abstract：:Pursuing our effort for developing effective inhibitors of the cancer-related hCA IX isoform, here we describe the synthesis of novel benzofuran-based carboxylic acid derivatives, featuring the benzoic (9a-f) or hippuric (11a,b) acid moieties linked to 2-methylbenzofuran or 5-bromobenzofuran tails via an ureido linker...

journal_title：ACS medicinal chemistry letters

authors： Eldehna WM,Nocentini A,Elsayed ZM,Al-Warhi T,Aljaeed N,Alotaibi OJ,Al-Sanea MM,Abdel-Aziz HA,Supuran CT

更新日期：2020-03-18 00:00:00

abstract：:Visible light-mediated photocatalysis, which relies on the ability of photocatalysts to absorb low-energy visible light and engage in single-electron transfer (SET) or energy transfer (ET) processes with organic substrates, has emerged as one of the fastest growing fields in organic synthesis. This catalytic platform ...

journal_title：ACS medicinal chemistry letters

authors： Li P,Terrett JA,Zbieg JR

更新日期：2020-09-21 00:00:00

abstract：:In this work, we present an investigation into the physical properties of a unique class of aromatic boronic acids, the benzoxaboroles. Using spectrophotometric methods, the ionization constants of a family of substituted benzoxaboroles are determined. Heterocyclic ring modifications are examined to determine their ef...

journal_title：ACS medicinal chemistry letters

authors： Tomsho JW,Pal A,Hall DG,Benkovic SJ

更新日期：2011-10-19 00:00:00

abstract：:A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for their inhibition on six human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms such as the physiologically relevant hCA I, II, VA, VB, VII, and IX and the X-ray complex in adduct with hCA II for some of them investigat...

journal_title：ACS medicinal chemistry letters

authors： Angeli A,di Cesare Mannelli L,Trallori E,Peat TS,Ghelardini C,Carta F,Supuran CT

更新日期：2018-04-09 00:00:00

abstract：:Here, we predicted the potential halogen bonding interaction between compound 2 and the 5-hydroxytryptamine 2B (5-HT2B) receptor and systematically assessed this interaction via structure-activity relationship analysis and molecular dynamics simulations. A physics-based computational protocol was then developed to fur...

journal_title：ACS medicinal chemistry letters

authors： Zhou Y,Wang Y,Li P,Huang XP,Qi X,Du Y,Huang N

更新日期：2018-10-01 00:00:00