New progesterone receptor antagonists: 3,3-disubstituted-5-aryloxindoles.

Abstract:

:A new series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this communication, the synthesis and structure-activity relationships (SARs) of various 3,3-substituents are discussed where it is clear that small alkyl and spiroalkyl groups are required to achieve better PR antagonist activity.

journal_name

Bioorg Med Chem Lett

authors

Fensome A,Bender R,Cohen J,Collins MA,Mackner VA,Miller LL,Ullrich JW,Winneker R,Wrobel J,Zhang P,Zhang Z,Zhu Y

doi

10.1016/s0960-894x(02)00746-1

subject

Has Abstract

pub_date

2002-12-02 00:00:00

pages

3487-90

issue

23

eissn

0960-894X

issn

1464-3405

pii

S0960894X02007461

journal_volume

12

pub_type

杂志文章
  • Phosphinic acid-based inhibitors of tubulin polyglutamylases.

    abstract::Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study descr...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.05.069

    authors: Liu Y,Garnham CP,Roll-Mecak A,Tanner ME

    更新日期:2013-08-01 00:00:00

  • Identification of Darmstoff analogs as selective agonists and antagonists of lysophosphatidic acid receptors.

    abstract::Darmstoff describes a family of gut smooth muscle-stimulating acetal phosphatidic acids initially isolated and characterized from the bath fluid of stimulated gut over 50 years ago. Despite similar structural and biological profiles, Darmstoff analogs have not previously been examined as potential LPA mimetics. Here, ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.08.096

    authors: Gududuru V,Zeng K,Tsukahara R,Makarova N,Fujiwara Y,Pigg KR,Baker DL,Tigyi G,Miller DD

    更新日期:2006-01-15 00:00:00

  • Optimization of allosteric MEK inhibitors. Part 2: Taming the sulfamide group balances compound distribution properties.

    abstract::Recently, we had identified an unexplored pocket adjacent to the known binding site of allosteric MEK inhibitors which allowed us to design highly potent and in vivo efficacious novel inhibitors. We now report that our initial preclinical candidate, featuring a phenoxy side chain with a sulfamide capping group, displa...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2015.11.004

    authors: Hartung IV,Hammer S,Hitchcock M,Neuhaus R,Scholz A,Siemeister G,Bohlmann R,Hillig RC,Pühler F

    更新日期:2016-01-01 00:00:00

  • Development of a selective and potent radioactive ligand for histamine H(3) receptors: A compound potentially useful for receptor occupancy studies.

    abstract::Radioligands are powerful tools for examining the pharmacological profiles of chemical leads and thus facilitate drug discovery. In this study, we identified and characterized 3-([1,1,1-(3)H]methyl)-2-(4-{[3-(1-pyrrolidinyl)propyl]oxy} phenyl)-4(3H)-quinazolinone ([(3)H]1) as a potent and selective radioligand for his...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.06.025

    authors: Mitobe Y,Ito S,Mizutani T,Nagase T,Sato N,Tokita S

    更新日期:2009-08-01 00:00:00

  • Identification of a stable chymase inhibitor using a pharmacophore-Based database search.

    abstract::In general, serine protease chymase inhibitors readily decompose in plasma. We previously found that thiazolidine-2,4-dione and thiadiazole derivatives are also unstable. Using a pharmacophore-based database search, we identified a benzo[b]thiophen-2-sulfonamide derivative as a stable chymase inhibitor. Finding a lead...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(02)00853-3

    authors: Koide Y,Tatsui A,Hasegawa T,Murakami A,Satoh S,Yamada H,Kazayama S,Takahashi A

    更新日期:2003-01-06 00:00:00

  • Regioselective synthesis and cytotoxicities of camptothecin derivatives modified at the 7-, 10- and 20-positions.

    abstract::A series of 7-acyloxymethylcamptothecin and 20-O-acyl-7-acyloxymethylcamptothecin derivatives were regioselectively prepared on different solvents. 7-Acyloxymethylcamptothecins possess more efficacy than 20-O-acyl-7-acyloxymethylcamptothecins against six human cancer cell lines in vitro. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2003.08.012

    authors: Pan XD,Han R,Sun PY

    更新日期:2003-11-03 00:00:00

  • Evaluation of licorice flavonoids as protein tyrosine phosphatase 1B inhibitors.

    abstract::Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator in insulin- and leptin-signaling cascades as well as a positive regulator in tumorigenesis, and much attention has been paid to PTP1B inhibitors as potential therapies for diabetes, obesity, and cancer. In the present study, the screening of a compo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.08.102

    authors: Li W,Li S,Higai K,Sasaki T,Asada Y,Ohshima S,Koike K

    更新日期:2013-11-01 00:00:00

  • Preparation of novel anthranilic acids as antibacterial agents: extensive evaluation of structural and physical properties on antibacterial activity and human serum albumin affinity.

    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 analogs ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.03.036

    authors: Thorarensen A,Li J,Wakefield BD,Romero DL,Marotti KR,Sweeney MT,Zurenko GE,Sarver RW

    更新日期:2007-06-01 00:00:00

  • Dual function inhibitors of relevance to chronic obstructive pulmonary disease.

    abstract::The general strategy and rationale underlying the design of COPD therapeutics that possess protease inhibitory activity and are also capable of releasing a species that attenuates inflammation by inhibiting caspase-1, are described. The synthesis and in vitro biochemical evaluation of a dual function molecule that seq...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.12.033

    authors: Dou D,He G,Alliston KR,Groutas WC

    更新日期:2011-05-15 00:00:00

  • The tert-butyl dimethyl silyl group as an enhancer of drug cytotoxicity against human tumor cells.

    abstract::In this study, we synthesized a series of enantiomerically pure (2R,3S)-disubstituted tetrahydropyranes with diverse functional groups using known methodologies. In addition to the tert-butyl dimethyl silyl group, other common protecting groups for hydroxyl groups such as allyl, acetate, and benzoate were used to obta...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.05.126

    authors: Donadel OJ,Martín T,Martín VS,Villar J,Padrón JM

    更新日期:2005-08-01 00:00:00

  • A new class of selective and potent inhibitors of neuronal nitric oxide synthase.

    abstract::The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound 3a from this series shows potent and selective inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(99)00432-1

    authors: Lowe JA 3rd,Qian W,Volkmann RA,Heck S,Nowakowski J,Nelson R,Nolan C,Liston D,Ward K,Zorn S,Johnson C,Vanase M,Faraci WS,Verdries KA,Baxter J,Doran S,Sanders M,Ashton M,Whittle P,Stefaniak M

    更新日期:1999-09-06 00:00:00

  • Structure activity relationships of benzylproline-derived inhibitors of the glutamine transporter ASCT2.

    abstract::The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.12.063

    authors: Singh K,Tanui R,Gameiro A,Eisenberg G,Colas C,Schlessinger A,Grewer C

    更新日期:2017-02-01 00:00:00

  • The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian alpha-carbonic anhydrase isoforms.

    abstract::The protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes that regulate cell growth, differentiation, migration and metabolism. Their inhibition was recently shown to constitute a new modality for treating cancers. Two clinically used PTK inhibitors (PTKIs), imatinib (Glivec/Gleevec) an...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.06.002

    authors: Parkkila S,Innocenti A,Kallio H,Hilvo M,Scozzafava A,Supuran CT

    更新日期:2009-08-01 00:00:00

  • Carbonic anhydrase inhibitors: Selective inhibition of the extracellular, tumor-associated isoforms IX and XII over isozymes I and II with glycosyl-thioureido-sulfonamides.

    abstract::A series of glycosyl-thioureido sulfonamides incorporating glucosamine, galactosamine, and mannosamine tails, and sulfanilamide, halogenosulfanilamide, and metanilamide heads was synthesized. Many of the new compounds showed micromolar-submicromolar affinity for the inhibition of the cytosolic isoforms I and II of the...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.07.019

    authors: Smaine FZ,Winum JY,Montero JL,Regainia Z,Vullo D,Scozzafava A,Supuran CT

    更新日期:2007-09-15 00:00:00

  • Discovery and structure-activity relationships of novel selective norepinephrine and dual serotonin/norepinephrine reuptake inhibitors.

    abstract::Novel arylthiomethyl morpholines are potent selective norepinephrine reuptake inhibitors (NERIs) and dual serotonin/norepinephrine reuptake inhibitors (SRI/NERIs). The target compounds were prepared using a stereochemically versatile synthesis featuring an aldol condensation as the key step. One enantiomer of the 2-me...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2004.11.025

    authors: Boot J,Cases M,Clark BP,Findlay J,Gallagher PT,Hayhurst L,Man T,Montalbetti C,Rathmell RE,Rudyk H,Walter MW,Whatton M,Wood V

    更新日期:2005-02-01 00:00:00

  • Synthesis of (Z)-2-((1H-indazol-3-yl)methylene)-6-[¹¹C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one as a new potential PET probe for imaging of the enzyme PIM1.

    abstract::(Z)-2-((1H-Indazol-3-yl)methylene)-6-methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one is a potent and selective proviral integration site in moloney murine leukemia virus kinase 1 (PIM1) inhibitor with an IC₅₀ value of 3 nM. (Z)-2-((1H-Indazol-3-yl)methylene)-6-[(11)C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.05.091

    authors: Gao M,Wang M,Miller KD,Zheng QH

    更新日期:2013-08-01 00:00:00

  • Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines. Part 2.

    abstract::A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives 8g, ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.05.004

    authors: Jung MH,El-Gamal MI,Abdel-Maksoud MS,Sim T,Yoo KH,Oh CH

    更新日期:2012-07-01 00:00:00

  • Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.

    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

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.03.104

    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

  • 2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 3: Synthesis and activity of isosteric analogs.

    abstract::Structure-activity relationships and efforts to optimize the pharmacokinetic profile of isosteric analogs of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among those examined, compound 25 showed potent affinity for cannabinoid receptor 1 (CB1) and receptor 2 (CB2). This comp...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2008.10.070

    authors: Kai H,Morioka Y,Koriyama Y,Okamoto K,Hasegawa Y,Hattori M,Koike K,Chiba H,Shinohara S,Iwamoto Y,Takahashi K,Tanimoto N

    更新日期:2008-12-15 00:00:00

  • Discovery of phenanthridine analogues as novel chemical probes disrupting the binding of DNA to ΔFosB homodimers and ΔFosB/JunD heterodimers.

    abstract::The transcription factor ΔFosB accumulates in response to chronic insults such as drugs of abuse, L-3,4-dihydroxyphenylalanine (l-DOPA) or stress in specific regions of the brain, triggering long lasting neural and behavioral changes that underlie aspects of drug addiction, dyskinesia, and depression. Thus, small mole...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127300

    authors: Li Y,Liu Z,Aglyamova G,Chen J,Chen H,Bhandari M,White MA,Rudenko G,Zhou J

    更新日期:2020-08-15 00:00:00

  • Substituted aminobenzimidazole pyrimidines as cyclin-dependent kinase inhibitors.

    abstract::A series of aminobenzimidazole-substituted pyrimidines were synthesized and evaluated for biochemical activity against CDK1. A high-speed parallel synthesis approach enabled the identification of a potent lead series having improved potency in the CDK1 assay (IC(50)<10nM). Cell cycle analysis showed that the compounds...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.02.076

    authors: Verma S,Nagarathnam D,Shao J,Zhang L,Zhao J,Wang Y,Li T,Mull E,Enyedy I,Wang C,Zhu Q,Altieri M,Jordan J,Dang TT,Reddy S

    更新日期:2005-04-15 00:00:00

  • New diarylureas and diarylamides possessing acet(benz)amidophenyl scaffold: design, synthesis, and antiproliferative activity against melanoma cell line.

    abstract::A series of new diarylurea and diarylamide derivatives possessing acet(benz)amidophenyl scaffold was synthesized. Their in vitro antiproliferative activity was tested against A375P human melanoma cell line. Compounds 1c,d and 2c,d showed the highest potencies with IC(50) values in sub-micromolar scale. In addition, co...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.03.020

    authors: Kim HJ,Cho HJ,Kim H,El-Gamal MI,Oh CH,Lee SH,Sim T,Hah JM,Yoo KH

    更新日期:2012-05-01 00:00:00

  • Topological estimation of electronic absorption bands of arene absorption spectra as a tool for modeling their toxicity and environmental pollution.

    abstract::A novel application of distance-based topological indices : Wiener (W)-, Szeged (Sz)-, Padmakar-Ivan (PI)-, and Sadhana (Sd)-indices in modeling electronic absorption bands of arene absorption spectra has been described. It is demonstrated that all these indices correlate linearly with the logarithm of beta and para e...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2004.06.094

    authors: Khadikar PV,Singh S,Jaiswal M,Mandloi D

    更新日期:2004-09-20 00:00:00

  • Nitrobenzene compounds inhibit expression of VCAM-1.

    abstract::A series of nitrobenzene compounds has been discovered as potent inhibitors of VCAM-1 expression and, therefore, potential drug candidates for autoimmune and allergic inflammatory diseases. Structure-activity relationship (SAR) studies showed that a nitro group and two other electron-withdrawing groups are essential f...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(01)00306-7

    authors: Meng CQ,Zheng XS,Holt LA,Hoong LK,Somers PK,Hill RR,Saxena U

    更新日期:2001-07-23 00:00:00

  • A facile synthesis, antibacterial activity of pulvinone and its derivatives.

    abstract::Pulvinone and several 3-fluoro-4-morpholino substituted pulvinone derivatives were synthesized in five steps from a common precursor, phenyl acetic acid. Most of synthetic morpholine substituted pulvinones showed inhibitory activity against Esherichia coli. For the first time, the inhibition of pulvinone and its deriv...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.11.090

    authors: Xu HW,Xu C,Fan ZQ,Zhao LJ,Liu HM

    更新日期:2013-02-01 00:00:00

  • New highly selective inhibitors of class II fructose-1,6-bisphosphate aldolases.

    abstract::Phosphoglycolo amidoxime and phosphoglycolo hydrazide, two new derivatives of phosphoglycolic acid, were synthesised and successfully tested as selective competitive inhibitors of class II FBP-aldolases. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2004.03.040

    authors: Fonvielle M,Weber P,Dabkowska K,Therisod M

    更新日期:2004-06-07 00:00:00

  • 4-Substituted (benzo[b]thiophene-2-carbonyl)guanidines as novel Na+/H+ exchanger isoform-1 (NHE-1) inhibitors.

    abstract::A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficac...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.04.046

    authors: Lee S,Lee H,Yi KY,Lee BH,Yoo SE,Lee K,Cho NS

    更新日期:2005-06-15 00:00:00

  • Mariannamides A and B, new cyclic octapeptides isolated from Mariannaea elegans NBRC102301.

    abstract::Two new cyclic octapeptides, mariannamides A (1) and B (2), have been isolated from Mariannaea elegans NBRC102301, a Pinus densiflora-derived filamentous fungus. Their structures were elucidated to be cyclo-(l-Leu1-l-Pro1-l-Pro2-l-Leu2-l-Ile1-l-Pro3-l-Val1-l-Ile2) and cyclo-(l-Leu1-l-Pro1-l-Pro2-l-Leu2-l-Ile1-l-Pro3-l...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2019.126946

    authors: Ishiuchi K,Hirose D,Kondo T,Watanabe K,Terasaka K,Makino T

    更新日期:2020-02-15 00:00:00

  • Discovery of tranylcypromine analogs with an acylhydrazone substituent as LSD1 inactivators: Design, synthesis and their biological evaluation.

    abstract::Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression, has been reported to be up-regulated and involved in numbers of solid malignant tumors. In this study, we identified a series of phenylalanyl hydrazones ba...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2017.10.003

    authors: Sun K,Peng JD,Suo FZ,Zhang T,Fu YD,Zheng YC,Liu HM

    更新日期:2017-11-15 00:00:00

  • CC chemokine receptor-3 (CCR3) antagonists: improving the selectivity of DPC168 by reducing central ring lipophilicity.

    abstract::DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2D6 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.03.065

    authors: Pruitt JR,Batt DG,Wacker DA,Bostrom LL,Booker SK,McLaughlin E,Houghton GC,Varnes JG,Christ DD,Covington M,Das AM,Davies P,Graden D,Kariv I,Orlovsky Y,Stowell NC,Vaddi KG,Wadman EA,Welch PK,Yeleswaram S,Solomon KA

    更新日期:2007-06-01 00:00:00