Synthesis and biological activity of trans-2,3-dihydroraloxifene.

abstract：:With the aim of improving HCV protease inhibitors reported in our previous manuscripts, we synthesized and evaluated a series of 1a-based tetrapeptidyl alpha-ketoamides with additional P4 modification. The promising analog discovered through this SAR, 5a, was further derivatized at P1' or P1 position. As a result of t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yip Y,Victor F,Lamar J,Johnson R,Wang QM,Glass JI,Yumibe N,Wakulchik M,Munroe J,Chen SH

更新日期：2004-10-04 00:00:00

abstract：:Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cook BN,Bentzien J,White A,Nemoto PA,Wang J,Man CC,Soleymanzadeh F,Khine HH,Kashem MA,Kugler SZ Jr,Wolak JP,Roth GP,De Lombaert S,Pullen SS,Takahashi H

更新日期：2009-02-01 00:00:00

abstract：:A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory a...

journal_title：Bioorganic & medicinal chemistry letters

authors： He H,Wang X,Shi L,Yin W,Yang Z,He H,Liang Y

更新日期：2016-07-15 00:00:00

abstract：:Multivalent interactions play an essential role in molecular recognition in living systems. These effects were employed to target tumor cells using albumin clusters bearing ∼10 molecules of asparagine-linked glycans (N-glycans). Noninvasive near-infrared fluorescence imaging clearly revealed A431 tumors implanted in B...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ogura A,Tahara T,Nozaki S,Onoe H,Kurbangalieva A,Watanabe Y,Tanaka K

更新日期：2016-05-01 00:00:00

abstract：:A facile method for the construction of double bond between 3-ylidene oxindoles and α-azido ketones has been successfully accomplished with a mild base. This method features azido reduction with concomitant double bond formation to provide the new class of bioactive enamino-2-oxindoles. These new compounds were screen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar NP,Vanjari Y,Thatikonda S,Pooladanda V,Sharma P,Sridhar B,Godugu C,Kamal A,Shankaraiah N

更新日期：2018-12-01 00:00:00

abstract：:Spiro-carboxamides were identified as inhibitors of 11beta-hydroxysteroid-dehydrogenase type 1 by high-throughput screening. Structure-based drug design was used to optimise the initial hit yielding a sub-nanomolar IC(50) inhibitor (0.5nM) on human 11beta-HSD1 with a high binding efficiency index (BEI of 32.7) which w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lepifre F,Christmann-Franck S,Roche D,Leriche C,Carniato D,Charon C,Bozec S,Doare L,Schmidlin F,Lecomte M,Valeur E

更新日期：2009-07-01 00:00:00

abstract：:Twenty three side chain analogs of the crambescidin alkaloids were prepared from the corresponding pentacyclic zwitterionic core acid. In the crambescidin 800 and 657 series, potency increased with increasing chain length. In addition, substantial variations in tumor selectivity with structure were seen. Crambescidin ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aron ZD,Pietraszkiewicz H,Overman LE,Valeriote F,Cuevas C

更新日期：2004-07-05 00:00:00

abstract：:The B(6) vitamers have been shown to display beneficial therapeutic effects in cardiovascular related disorders. The design of novel antiplatelet agents using pyridoxine as a template has led to the discovery of a class of novel cardio- and cerebro-protective agents. The present study describes the synthesis of severa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang W,Yao J,Pham V,Whitney T,Froese D,Friesen A,Stang L,Xu C,Shuaib A,Diakur JM,Haque W

更新日期：2004-09-20 00:00:00

abstract：:A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker DP,DeCrescenzo G,Freskos J,Getman DP,Hockerman SL,Li M,Mehta P,Munie GE,Swearingen C

更新日期：2001-10-22 00:00:00

abstract：:The selective inhibition of coagulation factor Xa has emerged as an attractive strategy for the discovery of novel antithrombotic agents. Here we describe highly potent benzamidine factor Xa inhibitors based on a vicinally-substituted heterocyclic core. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fevig JM,Pinto DJ,Han Q,Quan ML,Pruitt JR,Jacobson IC,Galemmo RA Jr,Wang S,Orwat MJ,Bostrom LL,Knabb RM,Wong PC,Lam PYS,Wexler RR

更新日期：2001-03-12 00:00:00

abstract：:A urokinase targeting conjugate of 2'-deoxy-5-fluorouridine (5-FUdr) was synthesized and tested for tumor-cell selective cytotoxicity in vitro. The 5-FUdr prodrug 2'-deoxy-5-fluoro-3'-O-(3-carboxypropanoyl)uridine (5-FUdrsuccOH) containing an ester-labile succinate linker was attached to the specific urokinase inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vine KL,Locke JM,Bremner JB,Pyne SG,Ranson M

更新日期：2010-05-01 00:00:00

abstract：:N-substituted chitosan and quaternized chitosan were synthesized and their antioxidant activity against hydroxyl radicals was assessed, respectively. Compared with the antioxidant activity of chitosan, the results indicated that the two kinds of chitosan derivatives had different scavenging ability on hydroxyl radical...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guo Z,Liu H,Chen X,Ji X,Li P

更新日期：2006-12-15 00:00:00

abstract：:Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is a novel therapeutic target for the treatment of inflammation and pain. In the preceding letter, we detailed the discovery of clinical candidate PF-04693627, a potent mPGES-1 inhibitor possessing a novel benzoxazole structure. While PF-04693627 was undergoing furthe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Walker DP,Arhancet GB,Lu HF,Heasley SE,Metz S,Kablaoui NM,Franco FM,Hanau CE,Scholten JA,Springer JR,Fobian YM,Carter JS,Xing L,Yang S,Shaffer AF,Jerome GM,Baratta MT,Moore WM,Vazquez ML

更新日期：2013-02-15 00:00:00

abstract：:A novel series of 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolines was synthesized and their TbetaR-1 inhibitory, p38 MAPK inhibitory, and TbetaR-1-dependent cellular activity were evaluated. Compound 5a was found to be a highly potent in the enzyme assay and TbetaR-1-dependent cellular ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li HY,Wang Y,Yan L,Campbell RM,Anderson BD,Wagner JR,Yingling JM

更新日期：2004-07-05 00:00:00

abstract：:A series of benzoxazole/benzothiazole-2,3-dihydrobenzo[b][1,4]dioxine derivatives (5a-5d and 8a-8j) was synthesized. Compounds were evaluated for binding affinities at the 5-HT1A and 5-HT2A receptors. Antidepressant activities of the compounds were screened using the forced swimming test (FST) and the tail suspension ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang S,Chen Y,Zhao S,Xu X,Liu X,Liu BF,Zhang G

更新日期：2014-04-01 00:00:00

abstract：:A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang SG,Kong LY,Li YH,Cheng XY,Su F,Tang S,Bi CW,Jiang JD,Li YH,Song DQ

更新日期：2015-09-01 00:00:00

abstract：:The use of chitosan as the wall of microcapsule designed for delivery of encapsulated celecoxib is reported. Microcapsules were characterised with respect to size and encapsulation efficiency of celecoxib. In vivo animals demonstrated that both free celecoxib administration and chitosan/celecoxib microcapsules adminis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheng SY,Yuen MC,Lam PL,Gambari R,Wong RS,Cheng GY,Lai PB,Tong SW,Chan KW,Lau FY,Kok SH,Lam KH,Chui CH

更新日期：2010-07-15 00:00:00

abstract：:Our attempts to prepare indolyl acid (3), enroute to prenostodione (2), from phenyl-hydrazine following a reported procedure of Fischer-Indole synthesis rather lead to ethyl 2-(5-oxo-1-phenyl-2,5-dihydro-1H-pyrazol-3-yl)acetate as a major product, which underwent facile condensation with aldehydes to provide the pyraz...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rasapalli S,Fan Y,Yu M,Rees C,Harris JT,Golen JA,Jasinski JP,Rheingold AL,Kwasny SM,Opperman TJ

更新日期：2013-06-01 00:00:00

abstract：:Telomeric G-rich single-stranded DNA can adopt a G-tetraplex structure which has been shown to inhibit telomerase activity. We have examined benzoindoloquinolines derivatives for their ability to stabilize an intramolecular G-quadruplex. The increase in T(m) value of the G-quadruplex was associated with telomerase inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alberti P,Schmitt P,Nguyen CH,Rivalle C,Hoarau M,Grierson DS,Mergny JL

更新日期：2002-04-08 00:00:00

abstract：:The relaxin family peptide receptors have been implicated in numerous physiological processes including energy homeostasis, cardiac function, wound healing, and reproductive function. Two family members, RXFP3 and RXFP4, are class A GPCRs with endogenous peptide ligands (relaxin-3 and insulin-like peptide 5 (INSL5), r...

journal_title：Bioorganic & medicinal chemistry letters

authors： DeChristopher B,Park SH,Vong L,Bamford D,Cho HH,Duvadie R,Fedolak A,Hogan C,Honda T,Pandey P,Rozhitskaya O,Su L,Tomlinson E,Wallace I

更新日期：2019-04-15 00:00:00

abstract：:Potent cyclin dependent kinase inhibitors were prepared using parallel synthesis methodology. Treating advanced intermediate 2 with a variety of hydrazides in DMSO at 80 degrees C for 30 min gave the desired acylsemicarbazides in good to excellent yield. Several compounds were active against cdk4/D1 and cdk2/E in the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nugiel DA,Vidwans A,Dzierba CD

更新日期：2004-11-15 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：:Potent and selective dipeptidyl boronic acid proteasome inhibitors are described. As compared to peptidyl aldehyde compounds, boronic acids in this series display dramatically enhanced potency. Compounds such as 15 are promising new therapeutics for treatment of cancer and inflammatory diseases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adams J,Behnke M,Chen S,Cruickshank AA,Dick LR,Grenier L,Klunder JM,Ma YT,Plamondon L,Stein RL

更新日期：1998-02-17 00:00:00

abstract：:Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron(III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhou T,Chen K,Kong LM,Liu MS,Ma YM,Xie YY,Hider RC

更新日期：2018-08-01 00:00:00

abstract：:Two reactive metabolites were identified in vivo for the dual A(2A)/A(1) receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shook BC,Rassnick S,Chakravarty D,Wallace N,Ault M,Crooke J,Barbay JK,Wang A,Leonard K,Powell MT,Alford V,Hall D,Rupert KC,Heintzelman GR,Hansen K,Bullington JL,Scannevin RH,Carroll K,Lampron L,Westover L,Russell

更新日期：2010-05-01 00:00:00

abstract：:Antagonists of the integrin receptor alpha(v)beta(3) are expected to have utility in the treatment of osteoporosis through inhibition of bone resorption. A series of potent, chain-shortened, pyrrolidinone-containing alpha(v)beta(3) receptor antagonists is described. Two sets of diasteromeric pairs of high-affinity ant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perkins JJ,Duong LT,Fernandez-Metzler C,Hartman GD,Kimmel DB,Leu CT,Lynch JJ,Prueksaritanont T,Rodan GA,Rodan SB,Duggan ME,Meissner RS

更新日期：2003-12-15 00:00:00

abstract：:A 2-pyrrolidinone ring containing a single hydroxymethyl side chain effectively replaces the N-acetylamino group of 4-(N-acetylamino)-3-guanidinobenzoic acid, a low micromolar inhibitor of influenza neuraminidase. This novel structural template affords new opportunities to evolve more potent benzoic acid inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brouillette WJ,Atigadda VR,Luo M,Air GM,Babu YS,Bantia S

更新日期：1999-07-19 00:00:00

abstract：:Structure-activity relationship studies for two series of 2-benzyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyridines having either a 3-cyano or 3-carboxamide moiety resulted in the preparation of the 2-(3,4-difluorobenzyloxy)-3-nitrile analog 10d and the 2-(3,4-difluorobenzyloxy)-3-(N-propylcarboxamide) analog 16c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meurer LC,Finke PE,Mills SG,Walsh TF,Toupence RB,Debenham JS,Goulet MT,Wang J,Tong X,Fong TM,Lao J,Schaeffer MT,Chen J,Shen CP,Sloan Stribling D,Shearman LP,Strack AM,Van der Ploeg LH

更新日期：2005-02-01 00:00:00

abstract：:A total of 24 pirfenidone derivatives were designed, synthesized and evaluated for their inhibitory activity against the human lung fibroblast cell line MRC-5. These compounds showed the remarkable proliferation inhibition against MRC-5 compared to pirfenidone as the positive control. The possible mechanism of this ki...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma Z,Pan Y,Huang W,Yang Y,Wang Z,Li Q,Zhao Y,Zhang X,Shen Z

更新日期：2014-01-01 00:00:00

abstract：:The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described. Prodrug 9 possesses a good lipophilicity (log P = 2.153 +/- 0.017), is stable in aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cingolani GM,Di Stefano A,Mosciatti B,Napolitani F,Giorgioni G,Ricciutelli M,Claudi F

更新日期：2000-06-19 00:00:00