Binding evaluation of fragment-based scaffolds for probing allosteric enzymes.

abstract：:cKIT kinase inhibitors, e.g., imatinib, could induce drug-acquired mutations such as cKIT T670I that rendered drug resistance after chronic treatment. Through a type II kinase inhibitor design approach we discovered a highly potent type II cKIT kinase inhibitor compound 35 (CHMFL-KIT-8140), which potently inhibited bo...

journal_title：Journal of medicinal chemistry

authors： Li B,Wang A,Liu J,Qi Z,Liu X,Yu K,Wu H,Chen C,Hu C,Wang W,Wu J,Hu Z,Ye L,Zou F,Liu F,Wang B,Wang L,Ren T,Zhang S,Bai M,Zhang S,Liu J,Liu Q

更新日期：2016-09-22 00:00:00

abstract：:A series of N-substituted 3-aminoglutarimides have been synthesized and tested for inhibitory activity against a range of chemokines in vitro and for suppression of lipopolysaccharide-induced inflammation in vivo. The results show that they represent the first class of small molecules with broad-spectrum chemokine inh...

journal_title：Journal of medicinal chemistry

authors： Fox DJ,Reckless J,Warren SG,Grainger DJ

更新日期：2002-01-17 00:00:00

abstract：:The synthesis of analogues of the antipsychotic drug butaclamol bearing chloro substituents on the benzene rings is described. On the basis of a perceived topographical similarity of a putative chlorophenylethylamine pharmacophore present in these analogues and in VUFB-10032 and doclothepin, agents related to octoclot...

journal_title：Journal of medicinal chemistry

authors： Humber LG,Sideridis N,Asselin AA,Bruderlein FT,Voith K

更新日期：1978-12-01 00:00:00

abstract：:Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrat...

journal_title：Journal of medicinal chemistry

authors： Hampton A,Slotin LA,Kappler F,Sasaki T,Perini F

更新日期：1976-12-01 00:00:00

abstract：:Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) ...

journal_title：Journal of medicinal chemistry

authors： Wen X,Sun H,Liu J,Cheng K,Zhang P,Zhang L,Hao J,Zhang L,Ni P,Zographos SE,Leonidas DD,Alexacou KM,Gimisis T,Hayes JM,Oikonomakos NG

更新日期：2008-06-26 00:00:00

abstract：:Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, the use of nonantibiotic molecules to block resistance mechanisms is a powerful alternative. Bacterial efflux pumps exert an early step in AMR development by allowing bacteria to grow at subinhibitor...

journal_title：Journal of medicinal chemistry

authors： Felicetti T,Cannalire R,Pietrella D,Latacz G,Lubelska A,Manfroni G,Barreca ML,Massari S,Tabarrini O,Kieć-Kononowicz K,Schindler BD,Kaatz GW,Cecchetti V,Sabatini S

更新日期：2018-09-13 00:00:00

abstract：:S1P5 is one of 5 receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood-brain barrier, where it maintains barrier integrity in in vitro models (J. Neuroinflamm. 2012, 9, 133). Little more is known about the effects of S1P5 modulation due to the absence of tool molecules wit...

journal_title：Journal of medicinal chemistry

authors： Hobson AD,Harris CM,van der Kam EL,Turner SC,Abibi A,Aguirre AL,Bousquet P,Kebede T,Konopacki DB,Gintant G,Kim Y,Larson K,Maull JW,Moore NS,Shi D,Shrestha A,Tang X,Zhang P,Sarris KK

更新日期：2015-12-10 00:00:00

abstract：:A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted-N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Cheng JC,Ishiguro K,Sartorelli AC

更新日期：1985-09-01 00:00:00

abstract：:Novel tumor-targeting theranostic conjugates 1 and 2, bearing either a fluorine-labeled prosthetic as a potential (18)F-PET radiotracer (1) or a fluorescence probe (2) for internalization studies in vitro, were designed and synthesized. We confirmed efficient internalization of 2 in biotin-receptor positive (BR+) canc...

journal_title：Journal of medicinal chemistry

authors： Vineberg JG,Wang T,Zuniga ES,Ojima I

更新日期：2015-03-12 00:00:00

abstract：:In this study, a new series of more than 60 quinoline derivatives has been synthesized and evaluated against Mycobacterium tuberculosis (H37Rv). Apart from the SAR exploration around the initial hits, the optimization process focused on the improvement of the physicochemical properties, cytotoxicity, and metabolic sta...

journal_title：Journal of medicinal chemistry

authors： Pitta E,Rogacki MK,Balabon O,Huss S,Cunningham F,Lopez-Roman EM,Joossens J,Augustyns K,Ballell L,Bates RH,Van der Veken P

更新日期：2016-07-28 00:00:00

abstract：:A series of 62 diarylamidine derivatives was evaluated for their antiproteolytic activity. In all but two of the compounds one or both of the amidino-substituted aryl moieties was either an indole or an indole-like ring. The latter included indene, benzimidazole, benzofuran, benzol[beta]thiophene, and several other re...

journal_title：Journal of medicinal chemistry

authors： Tidwell RR,Geratz JD,Dann O,Volz G,Zeh D,Loewe H

更新日期：1978-07-01 00:00:00

abstract：:The standard of care for HIV-1 infection, highly active antiretroviral therapy (HAART), combines two or more drugs from at least two classes. Even with the success of HAART, new drugs with novel mechanisms are needed to combat viral resistance, improve adherence, and mitigate toxicities. Active site inhibitors of HIV-...

journal_title：Journal of medicinal chemistry

authors： Li G,Meanwell NA,Krystal MR,Langley DR,Naidu BN,Sivaprakasam P,Lewis H,Kish K,Khan JA,Ng A,Trainor GL,Cianci C,Dicker IB,Walker MA,Lin Z,Protack T,Discotto L,Jenkins S,Gerritz SW,Pendri A

更新日期：2020-03-12 00:00:00

abstract：:The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride...

journal_title：Journal of medicinal chemistry

authors： Bamford MJ,Coe PL,Walker RT

更新日期：1990-09-01 00:00:00

abstract：:(R)-PCEP (3-amino-3-carboxypropyl-2'-carboxyethyl phosphinic acid, 1), a new metabotropic glutamate receptor 4 (mGlu4R) agonist, was discovered in a previously reported virtual screening. The (S)-enantiomer and a series of derivatives were synthesized and tested on recombinant mGlu4 receptors. A large number of deriva...

journal_title：Journal of medicinal chemistry

authors： Selvam C,Oueslati N,Lemasson IA,Brabet I,Rigault D,Courtiol T,Cesarini S,Triballeau N,Bertrand HO,Goudet C,Pin JP,Acher FC

更新日期：2010-04-08 00:00:00

abstract：:Dihydrofuro[3,4-c]pyridinones are the first class of small molecules reported to inhibit the cytolytic effects of the lymphocyte toxin perforin. A lead structure was identified from a high throughput screen, and a series of analogues were designed and prepared to explore structure-activity relationships around the cor...

journal_title：Journal of medicinal chemistry

authors： Lena G,Trapani JA,Sutton VR,Ciccone A,Browne KA,Smyth MJ,Denny WA,Spicer JA

更新日期：2008-12-11 00:00:00

abstract：:We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our i...

journal_title：Journal of medicinal chemistry

authors： Palani A,Shapiro S,Josien H,Bara T,Clader JW,Greenlee WJ,Cox K,Strizki JM,Baroudy BM

更新日期：2002-07-04 00:00:00

abstract：:The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need for additional antimicrobial agents....

journal_title：Journal of medicinal chemistry

authors： Vooturi SK,Cheung CM,Rybak MJ,Firestine SM

更新日期：2009-08-27 00:00:00

abstract：:A series of 6-substituted purinyl alkoxycarbonyl amino acids were synthesized and evaluated for their ability to stimulate cytotoxic T lymphocytes (CTLs) and the mixed lymphocyte reaction (MLR). A few of these compounds, in particular [[5-[6-(N,N-dimethylamino)purin-9-yl]pentoxy]-carbonyl]D-arginine (BCH-1393, 4a), di...

journal_title：Journal of medicinal chemistry

authors： Zacharie B,Gagnon L,Attardo G,Connolly TP,St-Denis Y,Penney CL

更新日期：1997-08-29 00:00:00

abstract：:A series of conformationally restricted congeners of pentamidine in which the flexible pentyl bridge of pentamidine was replaced by trans-1,2-bismethylenecyclopropyl, phenyl, pyridinyl, piperazinyl, homopiperazinyl, and piperidinyl groups were synthesized. The compounds were evaluated for trypanocidal activity in vitr...

journal_title：Journal of medicinal chemistry

authors： Donkor IO,Huang TL,Tao B,Rattendi D,Lane S,Vargas M,Goldberg B,Bacchi C

更新日期：2003-03-13 00:00:00

abstract：:Androgens are well-known to stimulate prostate cancer (PC) growth. Thus, blockade of androgen production in testes and adrenals by CYP17 inhibition is a promising strategy for the treatment of PC. Moreover, many PC patients suffer from glucocorticoid overproduction, and importantly mutated androgen receptors can be st...

journal_title：Journal of medicinal chemistry

authors： Hu Q,Jagusch C,Hille UE,Haupenthal J,Hartmann RW

更新日期：2010-08-12 00:00:00

abstract：:For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which in...

journal_title：Journal of medicinal chemistry

authors： Neyts J,De Clercq E,Singha R,Chang YH,Das AR,Chakraborty SK,Hong SC,Tsay SC,Hsu MH,Hwu JR

更新日期：2009-03-12 00:00:00

abstract：:A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro K(i) values ranged from 0.05 nM to >100 nM. (R)-N-(2-Fluoroethyl)-3-pi...

journal_title：Journal of medicinal chemistry

authors： Skaddan MB,Kilbourn MR,Snyder SE,Sherman PS,Desmond TJ,Frey KA

更新日期：2000-11-16 00:00:00

abstract：:Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding m...

journal_title：Journal of medicinal chemistry

authors： Xiao Z,Chen D,Song S,van der Vlag R,van der Wouden PE,van Merkerk R,Cool RH,Hirsch AKH,Melgert BN,Quax WJ,Poelarends GJ,Dekker FJ

更新日期：2020-10-22 00:00:00

abstract：:Two routes for the synthesis of 6-substtituted 8-azaguanosine analogues are described. 2,5,6-Triamino-4(3H)-pyrimidinethione (1) was converted by methylation, nitrosation, and acetylation to -n-acetyl-7-(methylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-5-amine (5). The reaction of 5 with 2,3,5-tri-O-acetyl-D-ribofuranosy...

journal_title：Journal of medicinal chemistry

authors： Elliot RD,Montgomery JA

更新日期：1976-10-01 00:00:00

abstract：:The DNA-intercalating agent amsacrine is an effective drug for the treatment of human leukemias and lymphomas but has minimal solid tumor activity. As a first step in identifying analogues with a wider spectrum of activity, a comparison was made of the in vivo antileukemic (P-388) activity of amsacrine analogues given...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Atwell GJ,Baguley BC

更新日期：1984-03-01 00:00:00

abstract：:A series of tricyclic analogues of 9-oxo-9H-xanthene-4-acetic acid have been prepared and evaluated for their ability to cause hemorrhagic necrosis in subcutaneously implanted colon 38 tumors in mice, in an effort to extend the structure-activity relationships for this series. As was found previously with analogues of...

journal_title：Journal of medicinal chemistry

authors： Rewcastle GW,Atwell GJ,Palmer BD,Boyd PD,Baguley BC,Denny WA

更新日期：1991-02-01 00:00:00

abstract：:Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based...

journal_title：Journal of medicinal chemistry

authors： Li S,Xu H,Cui S,Wu F,Zhang Y,Su M,Gong Y,Qiu S,Jiao Q,Qin C,Shan J,Zhang M,Wang J,Yin Q,Xu M,Liu X,Wang R,Zhu L,Li J,Xu Y,Jiang H,Zhao Z,Li J,Li H

更新日期：2016-07-28 00:00:00

abstract：:Novel 3,5-bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones (3a-e) display potent cytotoxicity and a preferential lethality toward various neoplasms compared to some normal cells. The corresponding sulfonic acid analogues 5a-e and an isostere 4 demonstrated substantially lower activity. The leads 3d...

journal_title：Journal of medicinal chemistry

authors： Das U,Pati HN,Sakagami H,Hashimoto K,Kawase M,Balzarini J,De Clercq E,Dimmock JR

更新日期：2011-05-12 00:00:00

abstract：:A series of biphenyl analogues of the new tuberculosis drug PA-824 was prepared, primarily by coupling the known (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-ol with iodobenzyl halides, followed by Suzuki coupling of these iodides with appropriate arylboronic acids or by assembly of the complete biaryl side...

journal_title：Journal of medicinal chemistry

authors： Palmer BD,Thompson AM,Sutherland HS,Blaser A,Kmentova I,Franzblau SG,Wan B,Wang Y,Ma Z,Denny WA

更新日期：2010-01-14 00:00:00

abstract：:Several known alpha-amino acid analogues and a new compound, N-chloroacetylphosphoramidate, a carbamyl phosphate analogue, were screened as antitumor agents. All gave 50% growth inhibition of cultures of human epidemeroid carcinoma of the nasopharynx at dosage levels of 2-8 mug/ml while showing no activity against L12...

journal_title：Journal of medicinal chemistry

authors： Glover GI,Nelson SO,Kaeder GR

更新日期：1977-03-01 00:00:00