Discovery of a novel olefin derivative as a highly potent and selective acetyl-CoA carboxylase 2 inhibitor with in vivo efficacy.

abstract：:Two cyclopropanecarbonyl derivatives were independently found to be 15 and 14 times more potent than the corresponding isopropylcarbonyl analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase and dihydroorotate dehydrogenase, respectively. A thorough examination of the co-crystal structures of available enzyme...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kuo PY,Shie TL,Chen YS,Lai JT,Yang DY

更新日期：2006-12-01 00:00:00

abstract：:Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujishiro S,Dodo K,Iwasa E,Teng Y,Sohtome Y,Hamashima Y,Ito A,Yoshida M,Sodeoka M

更新日期：2013-02-01 00:00:00

abstract：:The 5-HT3 receptor antagonist tropisetron (ICS 205-930) was found to be a potent and selective partial agonist at alpha7 nicotinic receptors. Two other 5-HT3 receptor antagonists, ondansetron and LY-278,584, were found to lack high affinity at the alpha7 nicotinic receptor. Quinuclidine analogues (1 and 2) of tropiset...

journal_title：Bioorganic & medicinal chemistry letters

authors： Macor JE,Gurley D,Lanthorn T,Loch J,Mack RA,Mullen G,Tran O,Wright N,Gordon JC

更新日期：2001-02-12 00:00:00

abstract：:A high throughput screening campaign revealed compound 1 as a potent antagonist of the human CCK(1) receptor. Here, we report the syntheses and SAR studies of 1,5-diarylpyrazole analogs with various structural modifications of the alkane side chain of the molecule. The difference in affinity between the two enantiomer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gomez L,Hack MD,McClure K,Sehon C,Huang L,Morton M,Li L,Barrett TD,Shankley N,Breitenbucher JG

更新日期：2007-12-01 00:00:00

abstract：:This paper documents a serious problem met during the testing of Gi protein-activating properties of a new series of synthetic compounds by measuring the induced binding of [(35)S]GTPgammaS to different subtypes of Gi protein. The problem arose from the strong affinity between [(35)S]GTPgammaS and the tested compounds...

journal_title：Bioorganic & medicinal chemistry letters

authors： Manetti D,Di Cesare Mannelli L,Dei S,Guandalini L,Martini E,Banchelli M,Ghelardini C

更新日期：2009-04-15 00:00:00

abstract：:Metabolites of the potent DP antagonist, MK-0524, were generated using in vitro systems including hepatic microsomes and hepatocytes. Four metabolites (two hydroxylated diastereomers, a ketone and an acyl glucuronide) were characterized by LC-MS/MS and 1H NMR. Larger quantities of these metabolites were prepared by ei...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nicoll-Griffith DA,Seto C,Aubin Y,Lévesque JF,Chauret N,Day S,Silva JM,Trimble LA,Truchon JF,Berthelette C,Lachance N,Wang Z,Sturino C,Braun M,Zamboni R,Young RN

更新日期：2007-01-15 00:00:00

abstract：:The structural modification of the benzylic ether region of oxime 1 has resulted in the identification of several novel aryl amides as selective or dual NK(1)/NK(2) antagonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shih NY,Albanese M,Anthes JC,Carruthers NI,Grice CA,Lin L,Mangiaracina P,Reichard GA,Schwerdt J,Seidl V,Wong SC,Piwinski JJ

更新日期：2002-01-21 00:00:00

abstract：:Novel (E)-N(1)-(benzyl)cinnamamidines were prepared and evaluated as NR2B subtype NMDA receptor ligands. Excellent affinity was achieved by appropriate substitution of either phenyl ring. The 2-methoxybenzyl compound 1h had approximately 1,000-fold lower IC(50) in NR2B than NR2A-containing cells. Replacement of the st...

journal_title：Bioorganic & medicinal chemistry letters

authors： Curtis NR,Diggle HJ,Kulagowski JJ,London C,Grimwood S,Hutson PH,Murray F,Richards P,Macaulay A,Wafford KA

更新日期：2003-02-24 00:00:00

abstract：:A series of N-acyl-N-hydroxy-beta-Phe were designed, synthesized, and shown to have potent inhibitory activity for carboxypeptidase A (CPA). They are the first examples of CPA inhibitors having a hydroxamate functionality. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim DH,Jin Y

更新日期：1999-03-08 00:00:00

abstract：:The eryA gene of the bacterial pathogen Brucella abortus has been functionally expressed in Escherichia coli. The resultant EryA was shown to catalyze the ATP-dependent conversion of erythritol to L-erythritol-4-phosphate (L-E4P). The steady state kinetic parameters of this reaction were determined and the enzyme was ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lillo AM,Tetzlaff CN,Sangari FJ,Cane DE

更新日期：2003-02-24 00:00:00

abstract：:We have described herein the syntheses of three novel series of aromatic ring containing pseudomycin side-chain analogues. Preliminary biological evaluations of these analogues clearly indicate that it is possible to synthesize rigid pseudomycin side-chain analogues without compromising in vitro antifungal activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jamison J,Levy S,Sun X,Zeckner D,Current W,Zweifel M,Rodriguez M,Turner W,Chen SH

更新日期：2000-09-18 00:00:00

abstract：:A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzo[d] imidazole-5-carbohydrazides having different substitution on the arylidene part were synthesized in good yield. The core nucleus benzimidazole-5-carboxylate (5) was efficiently synthesized by 'one-pot' nitro reductive cyclization reaction betwe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vasantha K,Basavarajaswamy G,Vaishali Rai M,Boja P,Pai VR,Shruthi N,Bhat M

更新日期：2015-04-01 00:00:00

abstract：:Triptolide (TP) is a diterpene epoxide component extracted from Tripterygium wilfordii and has been shown to possess an impressive anticancer effect. However, TP has not yet entered any clinic trials due to the severe adverse effects that resulted from the off-target absorption and distribution found in animal studies...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lou D,Lou Z,Lin Y,Shangguan H,Lin Y,Luo Q,Zhang H,Lin G,Chen R,Kou L,Bao S

更新日期：2020-12-17 00:00:00

abstract：:Based on the findings that cholest-4-en-3-one, an intestinal metabolite of cholesterol, has an anti-obesity effect on animals, the structure-effect relationship of its 3-oxo derivatives and related compounds were investigated. Cholesten-3-ones, which possesses an enone structure with a carbonyl group at C3, markedly i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suzuki K,Shimizu T,Nakata T

更新日期：1998-08-18 00:00:00

abstract：:In our continuous efforts to identify and develop novel targeted cancer treatments, a new morpholino-thiazole scaffold active against PI3Kβ has been identified. This Letter reports the optimization of this compound class to develop PI3Kβ isoform-selective inhibitors with suitable pharmacological properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Certal V,Halley F,Virone-Oddos A,Filoche-Rommé B,Carry JC,Gruss-Leleu F,Bertin L,Guizani H,Pilorge F,Richepin P,Karlsson A,Charrier V,Abecassis PY,Vincent L,Nicolas JP,Lengauer C,Garcia-Echeverria C,Schio L

更新日期：2014-03-15 00:00:00

abstract：:Synthesis and biological evaluation of new chrysene derivatives aimed at the development of anticancer agents were carried out. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker FF,Banik BK

更新日期：1998-10-20 00:00:00

abstract：:Inhibition of intestinal brush border DMT1 offers a novel therapeutic approach to the prevention and treatment of disorders of iron overload. Several series of diaryl and tricyclic benzylisothiourea compounds as novel and potent DMT1 inhibitors were discovered from the original hit compound 1. These compounds demonstr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Z,Kodumuru V,Sviridov S,Liu S,Chafeev M,Chowdhury S,Chakka N,Sun J,Gauthier SJ,Mattice M,Ratkay LG,Kwan R,Thompson J,Cutts AB,Fu J,Kamboj R,Goldberg YP,Cadieux JA

更新日期：2012-08-01 00:00:00

abstract：:Heteroaromatic analogs of DMU-212 (8-15) have been synthesized and evaluated for their anti-cancer activity against a panel of 60 human cancer cell lines. These novel analogs contain a trans-3,4,5-trimethoxystyryl moiety attached to the C2 position of indole, benzofuran, benzothiazole or benzothiophene ring (8, 11, 13...

journal_title：Bioorganic & medicinal chemistry letters

authors： Penthala NR,Thakkar S,Crooks PA

更新日期：2015-07-15 00:00:00

abstract：:Analogues of the naturally occurring cyclic hydroxamate dealanylalahopcin, which is an inhibitor of procollagen prolyl-4-hydroxylase, were synthesised and shown to be inhibitors of the human hypoxia-inducible factor prolyl hydroxylases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schlemminger I,Mole DR,McNeill LA,Dhanda A,Hewitson KS,Tian YM,Ratcliffe PJ,Pugh CW,Schofield CJ

更新日期：2003-04-17 00:00:00

abstract：:A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu S,Sanchez TW,Liu Y,Yin Y,Neamati N,Zhao G

更新日期：2013-11-15 00:00:00

abstract：:A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA with selectivity over tPA and plasmin. Potency is enhanced by the presence of a 4-halo and a 7-aryl substituent, particularly when substituted by a 3-carboxylic acid group. Compound 13j (UK-356,202) combines excellent potency and selectivit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barber CG,Dickinson RP,Fish PV

更新日期：2004-06-21 00:00:00

abstract：:The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the tw...

journal_title：Bioorganic & medicinal chemistry letters

authors： Menchise V,De Simone G,Di Fiore A,Scozzafava A,Supuran CT

更新日期：2006-12-15 00:00:00

abstract：:A series of 2-phenoxy-indan-1-one derivatives have been designed, synthesized, and tested as acetylcholinesterase inhibitors. The most potent compound exhibited high AChE inhibitory activity (IC50 = 50 nM), and the molecular docking study indicated that it was nicely accommodated by AChE. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sheng R,Lin X,Li J,Jiang Y,Shang Z,Hu Y

更新日期：2005-09-01 00:00:00

abstract：:A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Z,Min Q,Huang H,Liu R,Zhu Y,Zhu Q

更新日期：2018-05-15 00:00:00

abstract：:In the past few years, a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected amide b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thorarensen A,Wakefield BD,Romero DL,Marotti KR,Sweeney MT,Zurenko GE,Rohrer DC,Han F,Bryant GL Jr

更新日期：2007-05-15 00:00:00

abstract：:A novel caspase-3 substrate N-Ac-DEVD-N'-MC-R110, which is a fluorogenic substrate cleavable in a single step, has been prepared. It has a significantly higher enzyme turnover rate and sensitivity for detecting caspase-3 activity both in solution and living cells than existing fluorogenic substrates. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang ZQ,Liao J,Diwu Z

更新日期：2005-05-02 00:00:00

abstract：:A series of 3-aminoquinazolinediones was synthesized and evaluated for its antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core was explored and the optimal substitutions were combined to give two compounds, 2r and 2s, with exceptional enzyme potency (IC50 = 0.2 microM) and activity against ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tran TP,Ellsworth EL,Sanchez JP,Watson BM,Stier MA,Showalter HD,Domagala JM,Shapiro MA,Joannides ET,Gracheck SJ,Nguyen DQ,Bird P,Yip J,Sharadendu A,Ha C,Ramezani S,Wu X,Singh R

更新日期：2007-03-01 00:00:00

abstract：:Potential prodrugs for the TRH-like tripeptide pGlu-Glu-Pro-NH(2) were synthesized either by esterifying the Glu side-chain of the parent peptide in solution with alcohols in the presence of resin-bound dicyclohexylcarbodiimide or by solid-phase peptide chemistry. Affinities of these ester prodrugs to lipid membranes ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prokai-Tatrai K,Nguyen V,Zharikova AD,Braddy AC,Stevens SM,Prokai L

更新日期：2003-03-24 00:00:00

abstract：:Covalent enzyme inhibitors constitute a highly important group of biologically active compounds, with numerous drugs available on the market. Although the discovery of inhibitors of urease, a urea hydrolyzing enzyme crucial for the survival of some human pathogens, is a field of medicinal chemistry that has grown in r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Macegoniuk K,Kowalczyk R,Rudzińska A,Psurski M,Wietrzyk J,Berlicki Ł

更新日期：2017-03-15 00:00:00

abstract：:Horner-Emmons reaction of 4"-dehydro-5-O-TBDMS-avermectin B(1a) with a variety of phosphorus ylides using LHMDS gave novel 4"-alkylidene avermectin derivatives in high yields. Further modifications led to derivatives bearing diverse functional groups. The new avermectin derivatives showed potent growth inhibitory acti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nagai K,Sunazuka T,Shiomi K,Harder A,Turberg A,Omura S

更新日期：2003-11-17 00:00:00