Diaminocyclobutenediones as potent and orally bioavailable CXCR2 receptor antagonists: SAR in the phenolic amide region.

abstract：:The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang N,Wang QH,Wang WQ,Wang J,Li F,Tan SP,Cheng MS

更新日期：2012-01-01 00:00:00

abstract：:We report examples of a series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) analogues 12-15 prepared from a common functionalized building block 11 that can be conveniently synthesized on a large scale and in optically pure form. Isoindoline analogue 15 is the most cytotoxic agent in this series, has the highest D...

journal_title：Bioorganic & medicinal chemistry letters

authors： Masterson LA,Croker SJ,Jenkins TC,Howard PW,Thurston DE

更新日期：2004-02-23 00:00:00

abstract：:2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50=150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Goto T,Shiina A,Yoshino T,Mizukami K,Hirahara K,Suzuki O,Sogawa Y,Takahashi T,Mikkaichi T,Nakao N,Takahashi M,Hasegawa M,Sasaki S

更新日期：2013-06-01 00:00:00

abstract：:A series of steroid-polyamine conjugates were synthesized and evaluated for their antimicrobial activity. This study was focused on the effect of stereochemistry at the C-3 and C-5 of steroids and types of polyamine at C-3 on activity against various human pathogens. All the conjugates exhibited strong antimicrobial a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim HS,Khan SN,Jadhav JR,Jeong JW,Jung K,Kwak JH

更新日期：2011-07-01 00:00:00

abstract：:Cell penetrating peptide TAT was introduced into doxorubicin structure. Synthesized doxorubicin-TAT conjugate showed different intracellular distribution pattern and cell killing activity from those of free doxorubicin. Unlike free doxorubicin, doxorubicin-TAT conjugate was highly permeable to drug-resistant cells and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liang JF,Yang VC

更新日期：2005-11-15 00:00:00

abstract：:The peptide ligase subtiligase, derived from subtilisin, has been employed in the identification of protein N-termini in complex mixtures. Here, the peptide ester substrates for the ligation reaction were optimized with respect to solubility, resulting in greater incorporation of the N-terminal tags. Additionally, the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoshihara HA,Mahrus S,Wells JA

更新日期：2008-11-15 00:00:00

abstract：:We have focused on the C5-modification of 2'-deoxyuridine with substituted heterocycles for bioactivity, such as antiviral or anticancer activity. Herein, we report a novel class of nucleoside analogues with perfluoroalkyltriazole moiety as an anticancer drug candidate. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SM,Yang H,Park SK,Kim HM,Kim BH

更新日期：2010-10-01 00:00:00

abstract：:Bruton's Tyrosine Kinase (BTK) is one of the crucial kinases for the B cell maturation and mast cell activation, and specific inhibitors of BTK are considered to be attractive targets in drug discovery research. In this Letter, we have designed and synthesized a new fluorescent probe for TR-FRET-based high-throughput ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Asami T,Kawahata W,Sawa M

更新日期：2015-01-01 00:00:00

abstract：:A series of novel 5-trans-hydroxyadamantan-2-yl-5,6,7,8-tetrahydropyrazolo[4,3-c]azepin-4(1H)-ones that inhibit 11beta-hydroxysteroid dehydrogenase type 1 are described. We discovered these 7-membered cyclic amide derivatives by introducing a distinctive linker through pharmacophore analysis of known ligands included ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Udagawa S,Sakami S,Takemura T,Sato M,Arai T,Nitta A,Aoki T,Kawai K,Iwamura T,Okazaki S,Takahashi T,Kaino M

更新日期：2013-03-15 00:00:00

abstract：:We synthesized pyrrolomorphinan derivatives 6, 7, and 9 to examine whether the pyrrole ring would be an accessory site in the kappa opioid receptor selective antagonist, nor-binaltorphimine. Derivative 6 had an alpha,beta-unsaturated ketone substituent that strongly bound to the kappa receptor. The compound with the h...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujii H,Ida Y,Hanamura S,Osa Y,Nemoto T,Nakajima M,Hasebe K,Nakao K,Mochizuki H,Nagase H

更新日期：2010-09-01 00:00:00

abstract：:A novel series of benzothiophene derivatives was discovered as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity relationship studies on high-throughput screening hit compound 1 led to the identification of 7-acetyl-3-methyl-N-(quinolin-2-yl)-1-benzothiophene-2-carboxamide (16), with potent inhibitory acti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kawamoto Y,Tomino M,Hiramatsu K,Oyama Y,Hayashi Y

更新日期：2019-06-01 00:00:00

abstract：:A series of alpha1a receptor antagonists derived from a 4-aryl-3,4-dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to picomolar range along with high selectivity was obtained. In vivo efficacy in a prostate contraction model in rats was observed with a few derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nantermet PG,Barrow JC,Selnick HG,Homnick CF,Freidinger RM,Chang RS,O'Malley SS,Reiss DR,Broten TP,Ransom RW,Pettibone DJ,Olah T,Forray C

更新日期：2000-08-07 00:00:00

abstract：:A single-step sensing system was developed to visually detect ligands of a cleavase-like RNA aptazyme at room temperature using aptazyme-tethered gold nanoparticles, the electrosteric stability of which was adjusted by increasing their diameter. In this system, the ligand induces self-cleavage of the aptazyme on gold ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ogawa A

更新日期：2011-01-01 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：:A series of 14-deoxy-11,12-didehydroandrographolide analogues were synthesized from naturally occurring andrographolide and their cytotoxicity evaluated against nine cancer cell lines including cholangiocarcinoma. Analogues 5a and 5b exhibited the most potent cytotoxicity with ED50s of 3.37 and 3.08 μM on KKU-M213 cel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sombut S,Bunthawong R,Sirion U,Kasemsuk T,Piyachaturawat P,Suksen K,Suksamrarn A,Saeeng R

更新日期：2017-12-01 00:00:00

abstract：:Currently, there is an ongoing interest in the synthesis of nucleoside diphosphate analogs as important regulators in catabolism/anabolism, and their potential applications as mechanistic probes and chemical tools for bioassays. However, the pyrophosphate bond formation step remains as the bottleneck. In this Digest, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Z

更新日期：2015-09-15 00:00:00

abstract：:A novel series of 3,5,6-trisubstituted pyrazolo[4,3-d]pyrimidin-7-one derivatives, especially 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-ones were synthesized and evaluated for their in vitro anticancer activities against various human cancer cell lines. The inhibitory activities for several kinases have also been ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Devegowda VN,Kim JH,Han KC,Yang EG,Choo H,Pae AN,Nam G,Choi KI

更新日期：2010-03-01 00:00:00

abstract：:Brønsted acid-induced fragmentation of a triazoline is used as a tool to identify Brønsted base additives capable of playing the role of a proton shuttle. Relative to water, dimethyl formamide accelerates proton transfer substantially under these conditions. A series of alcohols and ethers were also used to demonstrat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donahue MG,Hong KB,Johnston JN

更新日期：2009-09-01 00:00:00

abstract：:The resistance of pathogenic fungi and failure of drug therapy increased dramatically. Numerous studies have reported the individual or synergistic antifungal potency of natural and synthesized flavonoids, especially against drug-resistant fungi. This brief review summarizes the structure and individual or synergistic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin YS

更新日期：2019-10-01 00:00:00

abstract：:Pyrazolopyrimidines were discovered as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A. In addition to its intrinsic activity, compound 9n significantly enhances nicotinic acid binding to the receptor, thereby potentiating the functional efficacy of nicotinic acid. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shen HC,Taggart AK,Wilsie LC,Waters MG,Hammond ML,Tata JR,Colletti SL

更新日期：2008-09-15 00:00:00

abstract：:A novel series of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R) is reported. Members of this series have been identified, which exhibit sub-micromolar binding affinity for the MC4-R, functional potency <100nM, and good oral exposure in rat. Antagonists of the MC4-R are potentially u...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marsilje TH,Roses JB,Calderwood EF,Stroud SG,Forsyth NE,Blackburn C,Yowe DL,Miao W,Drabic SV,Bohane MD,Daniels JS,Li P,Wu L,Patane MA,Claiborne CF

更新日期：2004-07-16 00:00:00

abstract：:To improve the pharmacokinetics of a previously reported series of dipeptidyl nitrile cathepsin B inhibitors, the P(2)-P(3) amide group was replaced with an arylamine. Further optimization of this template resulted in highly potent and selective inhibitors with excellent oral availability. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Greenspan PD,Clark KL,Cowen SD,McQuire LW,Tommasi RA,Farley DL,Quadros E,Coppa DE,Du Z,Fang Z,Zhou H,Doughty J,Toscano KT,Wigg AM,Zhou S

更新日期：2003-11-17 00:00:00

abstract：:A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species, particularly hemiptera and lepidoptera. Mode-of-action studies showed that they act on nicotinic acetylcholine receptors (nAChRs) primarily as inhibitors. Here we rep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang W,Holyoke CW Jr,Barry J,Leighty RM,Cordova D,Vincent DR,Hughes KA,Tong MT,McCann SF,Xu M,Briddell TA,Pahutski TF,Lahm GP

更新日期：2016-11-15 00:00:00

abstract：:1,2,3,4-Tetrahydropyrazino[1,2-a]indoles are described as a novel class of I(2) imidazoline receptor ligands. In particular, 8-methoxy-1,2,3,4-tetrahydropyrazino[1,2-a]indole (8-OMe THPI; 3c) binds with high affinity at I(2) imidazoline receptors (K(i)=6.2 nM) and with exceptional (> or =1000-fold) selectivity relativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chang-Fong J,Tyacke RJ,Lau A,Westaway J,Hudson AL,Glennon RA

更新日期：2004-02-23 00:00:00

abstract：:A series of novel hybrid molecules 4a-y containing thiazole and benzotriazole templates were designed and synthesized. The structures of the synthesized compounds were elucidated by IR, (1)H NMR, (13)C NMR and mass spectral data. All the synthesized compounds were tested for their antimicrobial activity (zone of inhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gaikwad ND,Patil SV,Bobade VD

更新日期：2012-05-15 00:00:00

abstract：:β-Sitosterol is the most abundant plant sterol in the human diet. It is also the major component of several traditional medicines, including saw palmetto and devil's claw. Although β-sitosterol is effective against enlarged prostate in human clinical trials and has anti-cancer and anti-inflammatory activities, the mec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lomenick B,Shi H,Huang J,Chen C

更新日期：2015-11-01 00:00:00

abstract：:The C-3 substituents effect on NHE-1 inhibitory activity of (5-arylfuran-2-ylcarbonyl)guanidines, previously identified as potent NHE-1 inhibitors, was investigated. The introduction of amine or alkyl groups at the 3-position of the furan ring, next to the acylguanidine moiety, remarkably improves NHE-1 inhibitory pot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee S,Kim T,Lee BH,Yoo SE,Lee K,Yi KY

更新日期：2007-03-01 00:00:00

abstract：:Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as possible treatments for a range of conditions, including atherosclerosis, venous thrombosis, and obesity. We describe the synthesis and inhibitory activity of a novel series of compounds based on bis-arylsulfonamide and aryl sulfonimide ...

journal_title：Bioorganic & medicinal chemistry letters

authors： El-Ayache NC,Li SH,Warnock M,Lawrence DA,Emal CD

更新日期：2010-02-01 00:00:00

abstract：:The structures of the uracil and thiouracils were examined using NMR spectroscopy and crystal structure data when available. The relationships between the extent of polarization and the C5-C6 bond length as well as the H5-H6 coupling constants were probed. It was found that the bond length and coupling constants corre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang S,Gronert S,Wu W

更新日期：2011-11-01 00:00:00

abstract：:S1P(1) receptor driven lymphopenia has proven utility in the treatment of an array of autoimmune disease states. As a part of our efforts to develop potent and selective S1P(1) receptor agonists, we have identified a novel chemical series of 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acid S1P(1) r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Buzard D,Han S,Thoresen L,Moody J,Lopez L,Kawasaki A,Schrader T,Sage C,Gao Y,Edwards J,Barden J,Thatte J,Fu L,Solomon M,Liu L,Al-Shamma H,Gatlin J,Le M,Xing C,Espinola S,Jones RM

更新日期：2011-10-01 00:00:00