Structure-activity relationships of a novel class of Src SH2 inhibitors

Buchanan, Joan L.; Vu, Chi B.; Merry, Taylor; Corpuz, Evelyn G.; Pradeepan, Selvaluxmi G.; Mani, Ukti N.; Yang, Michael G.; Plake, Hilary R.; Varkhedkar, Vaibhav; Lynch, Berkley A.; MacNeil, Ian A.; Loiacono, Kara A.; Tiong, Choi Lai; Holt, Dennis A.

doi:10.1016/s0960-894x(99)00389-3

Cited by 49 publications

(38 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2,3-Dihydro-1,2,4-oxadiazoles exhibit a n C ¼ N between 1670 and 1676 cm À1 [156,183], while in 2,5-dihydro the same absorption is at 1622-1640 cm À1 [162,173]. …”

Section: Nmr Spectroscopymentioning

confidence: 95%

“…A wide variety of carboxylic acid derivatives can be used for the formation of Oacylated amidoximes, such as esters [196], acid chlorides [152,154,171,175,187,197], [197b, 152, 171, 198], including symmetrical acid anhydrides derived from amino acids [184c], and amino-acid activated as succinimides [183].…”

Section: Synthesismentioning

confidence: 99%

“…13.3.6 1,2,4-Oxadiazoles in Medicine 1,2,4-Oxadiazole ring occurs widely in biologically active synthetic compounds, and is often used in drug discovery as a hydrolysis-resisting bioisosteric replacement for amide or ester functionalities [283] because of its electronic properties. Its derivatives can be found in a vast number of compounds exerting biological activity, such as ligands of benzodiazepine receptors [284,285], anti-inflammatory agents [131,199,234], antiviral agents [283], inhibitors of protein tyrosine phosphatases [286], agonists of muscarinic receptors [287], inhibitors of Src SH2 [183], antagonists of histamine H 3 -receptors [288], integrin receptor antagonists [200], angiotensin II receptor antagonists [289], and HIV-1 reverse transcriptase inhibitors [290]. 1,2,4-Oxadiazole moieties have been used in the design of dipeptidomimetics as peptide building blocks [184a,b].…”

Section: Reactivity Of Substituentsmentioning

confidence: 99%

See 2 more Smart Citations

Oxadiazoles

Romeo¹,

Chiacchio²

2011

Modern Heterocyclic Chemistry

View full text Add to dashboard Cite

“…2,3-Dihydro-1,2,4-oxadiazoles exhibit a n C ¼ N between 1670 and 1676 cm À1 [156,183], while in 2,5-dihydro the same absorption is at 1622-1640 cm À1 [162,173]. …”

Section: Nmr Spectroscopymentioning

confidence: 95%

Section: Synthesismentioning

confidence: 99%

Section: Reactivity Of Substituentsmentioning

confidence: 99%

See 1 more Smart Citation

Oxadiazoles

Romeo¹,

Chiacchio²

2011

Modern Heterocyclic Chemistry

View full text Add to dashboard Cite

“…Researchers at ARIAD have conducted structure-based design studies examining various types of scaffolds for Src SH2 inhibitors, including ureido-type peptide mimetics [223], di-substituted thiazoles [224], oxazoles [220] and benzamide [225]. Notably, X-ray crystallography revealed the benzamide template forms hydrogen bonds with LysßDö, displacing water molecules found in the previous X-ray structure.…”

Section: Importance Of the Scaffoldmentioning

confidence: 99%

Probing the Tyrosine Phosphorylation State in Breast Cancer by Src Homology 2 Domain Binding

Mayer¹

2004

View full text Add to dashboard Cite

Pubhc reporting burden for Ms collection of information is estimated to average 1 hour per response, Including the lime for reviewing instructions, searching existing data sources gathering and maintaininn the data neededI andcompletingland renewing this collection of information. Send comments regarding this burden estimate or any other asped of this collection of InfoirnaBorf iffsSÄto" educing this burden to Washington Headquarters AUTHOR(S)Bruce J. Mayer PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University Abstract (Maximum 200 Words) (abstract should contain no proprietary or confidential information)Improved molecular diagnostic methods that can classify tumors and predict their response to therapy have enormous potential to improve the effectiveness breast cancer treatments. The overall goal of this project is to develop a novel molecular diagnostic method, i: termed SH2 profiling, that can classify cell samples based on their global protein tyrosine phosphorylation state. The first aim is to use an existing SH2 profiling method, based on far-Western blotting, to analyze fresh surgical breast cancer samples. The second aim is to o develop a more high-throughput quantitative reversed-phase SH2 profiling format, and test its usefulness in classifying breast cancer samples. The third aim is to develop histochemical SH2 profiling methods that can be used to analyze archived, formalin-fixed tissue sections, and perform pilot retrospective studies to determine whether SH2 binding patterns have potential prognostic value. In the past year we have made great progress in developing the reversed-phase array and histochemical SH2 profiling formats, and results suggest that these quantitative methods will be useful in classifying breast cancer samples. In the coming year, once HSRRB approval for use of human samples is secured, we will begin to apply these new methods to the analysis of actual breast cancer specimens. SUBJECT TERMS Conclusions 9References 10 Appendices 10-93Mayer, B.J. INTRODUCTIONThe focus is this study is to test whether a novel molecular diagnostic approach, SH2 profiling, can serve as a useful prognostic tool to classify breast cancer. SH2 domains are small protein modules that bind specifically to tyrosine phosphorylated peptides. These domains play an important role in normal signal transduction, mediating the formation of multiprotein complexes in response to changes in tyrosine phosphorylation [1,2]. There are ~116 SH2 domains in the human genome, and different SH2 domains recognize different tyrosine phosphorylated proteins. SH2 profiling is a method in which a battery SH2 domain probes is used to provide a snapshot of the global state of tyrosine phosphorylation in a cell sample [3,4]. Different breast cancers are likely to have different patterns of tyrosine phosphorylation, reflecting differences in the signal transduction pathways active in the tumor, and thus SH2 profiling has the potential to provide a biologically relevant means to classify these tumors. In this project we prop...

show abstract

“…21 The Buchanan group described a reaction between a Boc amino acid succinimidyl ester and simple amidoximes with the aid of EDCÁHOBt followed by cyclization in refluxing pyridine to obtain the corresponding 1,2,4-oxadiazole. 22 To the best of our knowledge, the synthesis of 1,2,4-oxadiazole-linked orthogonally protected dipeptide mimetics, which serve as building blocks for preparation of the corresponding oligopeptide mimetics, is yet to be reported. In the present work, the synthesis of 1,2,4-oxadiazole-linked N,N 0 -orthogonally protected dipeptide mimetics by coupling of an N-protected amino acid-derived amidoxime with another orthogonally protected amino acid fluoride followed by cyclization is described.…”

mentioning

confidence: 99%

Synthesis of 1,2,4-oxadiazole-linked orthogonally urethane-protected dipeptide mimetics

Sureshbabu

Hemantha

Naik

2008

Tetrahedron Letters

View full text Add to dashboard Cite

a b s t r a c tThe synthesis of a new class of 1,2,4-oxadiazole-linked orthogonally urethane-protected dipeptide mimetics is described. The protocol employs a reaction between an N-protected amino acyl fluoride and an amino acid-derived amidoxime. All the three commonly employed urethanes have been used in this protocol for N-protection. The course of the reaction was found to be high yielding and all new compounds were well characterized by NMR and mass spectroscopy. The O-acyl amidoxime intermediate has also been isolated as a stable solid.

show abstract

Structure-activity relationships of a novel class of Src SH2 inhibitors

Cited by 49 publications

References 16 publications

Oxadiazoles

Oxadiazoles

Probing the Tyrosine Phosphorylation State in Breast Cancer by Src Homology 2 Domain Binding

Synthesis of 1,2,4-oxadiazole-linked orthogonally urethane-protected dipeptide mimetics

Contact Info

Product

Resources

About