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Chemical Structure| 161043-38-5 Chemical Structure| 161043-38-5

Structure of 161043-38-5

Chemical Structure| 161043-38-5

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Product Citations

Product Citations

Henderson, Ian M. ; Zeng, Fanxun ; Bhuiyan, Nazmul H. ; Luo, Dan ; Martinez, Maria ; Smoake, Jane , et al.

Abstract: Interest in development of potent, selective inhibitors of the phosphatase from the receptor type protein tyrosine phosphatase PTPRD as antiaddiction agents is supported by human genetics, mouse models and studies of our lead compound PTPRD phosphatase inhibitor, 7-butoxy illudalic acid analog 1 (7-BIA). We now report structure-activity relationships for almost 70 7-BIA-related compounds and results that nominate a 7- cyclopentyl methoxy analog as a candidate for further development. While efforts to design 7-BIA analogs with substitutions for other parts failed to yield potent inhibitors of PTPRDs phosphatase, ten 7-position substituted analogs displayed greater potency at PTPRD than 7-BIA. Several were more selective for PTPRD vs the receptor type protein tyrosine phosphatases S, F and J or the nonreceptor type protein tyrosine phosphatase N1 (PTPRS, PTPRF, PTPRJ or PTPN1/PTP1B), phosphatases at which 7-BIA displays activity. In silico studies aided design of novel analogs. A 7-position cyclopentyl methoxy substituted 7-BIA analog termed NHB1109 displayed 600-700 nM potencies in inhibiting PTPRD and PTPRS, improved selectivity vs PTPRS, PTPRF, PTPRJ or PTPN1/PTP1B phosphatases, no substantial potency at other protein tyrosine phosphatases screened, no significant potency at any of the targets of clin.-useful drugs identified in EUROFINS screens and significant oral bioavailability. Oral doses up to 200 mg/kg were well tolerated by mice, though higher doses resulted in reduced weight and apparent ileus without clear organ histopathol. NHB1109 provides a good candidate to advance to in vivo studies in addiction paradigms and toward human use to reduce reward from addictive substances.

Keywords: Receptor type protein tyrosine phosphatase ; Cell adhesion molecule ; Addiction ; Drug reward ; Opiates ; Stimulants

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Product Details of [ 161043-38-5 ]

CAS No. :161043-38-5
Formula : C6H9Br
M.W : 161.04
SMILES Code : BrCC1(C2)CC2C1
MDL No. :MFCD20633000
InChI Key :ASZCSSCMSDFJJR-UHFFFAOYSA-N
Pubchem ID :91800902

Safety of [ 161043-38-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H314
Precautionary Statements:P210-P233-P240-P241-P242-P243-P260-P264-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P370+P378-P403+P235-P405-P501
Class:8(3)
UN#:2920
Packing Group:
 

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