Synthesis of 2‐phosphinoxidomethyl‐ and 2‐phosphonomethyl glutaric acid derivatives

Harsányi, Kálmán; Domány, György; Greiner, István; Forintos, Henrietta; Keglevich, György

doi:10.1002/hc.20142

Cited by 23 publications

(9 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, robust efforts are being carried out in several laboratories to improve on bioavailability and minimize potential toxicity. These include the development of prodrugs of 2-PMPA derivatives like phosphonate and phosphinate esters [136], more lipophilic and potent thiols [23], and the use of alternative zinc- binding functionalities such as hydroxamates [137]. Additional efforts in our laboratory are focused on creating new GCPII inhibitor structures employing alternative zinc binding groups which when used in other drugs have demonstrated oral bioavailability and drug like character in the clinic.…”

Section: Gcpii As a Therapeutic Targetmentioning

confidence: 99%

Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer

Bařinka

Rojas²,

Slusher³

et al. 2012

CMC

168

175

View full text Add to dashboard Cite

Glutamate carboxypeptidase II (GCPII) is a membrane-bound binuclear zinc metallopeptidase with the highest expression levels found in the nervous and prostatic tissue. Throughout the nervous system, glia-bound GCPII is intimately involved in the neuron-neuron and neuron-glia signaling via the hydrolysis of N-acetylaspartylglutamate (NAAG), the most abundant mammalian peptidic neurotransmitter. The inhibition of the GCPII-controlled NAAG catabolism has been shown to attenuate neurotoxicity associated with enhanced glutamate transmission and GCPII-specific inhibitors demonstrate efficacy in multiple preclinical models including traumatic brain injury, stroke, neuropathic and inflammatory pain, amyotrophic lateral sclerosis, and schizophrenia. The second major area of pharmacological interventions targeting GCPII focuses on prostate carcinoma; GCPII expression levels are highly increased in androgen-independent and metastatic disease. Consequently, the enzyme serves as a potential target for imaging and therapy. This review offers a summary of GCPII structure, physiological functions in healthy tissues, and its association with various pathologies. The review also outlines the development of GCPII-specific small-molecule compounds and their use in preclinical and clinical settings.

show abstract

Section: Gcpii As a Therapeutic Targetmentioning

confidence: 99%

Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer

Bařinka

Rojas²,

Slusher³

et al. 2012

CMC

168

175

View full text Add to dashboard Cite

show abstract

“…On the basis of our previous experiences with cyclic >P(O)H species [8,9], it was a challenge for us to convert them to the corresponding aminomethyl derivatives. 1,3,2-Dioxaphosphinane SCHEME 1 2-oxide 1 reacted easily with paraformaldehyde and secondary amines including pyrrolidine, morpholine, piperidine-, and piperazine derivatives at 55…”

Section: Introductionmentioning

confidence: 99%

Synthesis of cyclic aminomethylphosphonates and aminomethyl‐arylphosphinic acids by an efficient microwave‐mediated phospha‐mannich approach

Keglevich

Szekrényi

Sipos

et al. 2008

Heteroatom Chemistry

Self Cite

View full text Add to dashboard Cite

Microwave‐assisted condensation of 1,3,‐2‐dioxaphosphinane 2‐oxide (1), paraformaldehyde and secondary amines including 5‐ and 6‐membered N‐heterocycles at 55°C gave cyclic aminomethylphosphonates (2), whereas an analogous reaction involving dibenzo[c.e][1,2]oxaphosphinane 2‐oxide (3) resulted in the corresponding aminomethyl‐2‐(2′‐hydroxybiphenyl)phosphinic acids (4) as a consequence of a hydrolytic ring opening following the condensation. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:207–210, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20387

show abstract

“…In our laboratory, the possible accomplishments of the phosphaMichael reaction were studied on simple model reactions [4]. The addition of >P(O)H species to α-methyleneglutaric esters was performed to make available potential NAALADase inhibitors useful in the treatment of stroke [5]. The reaction of a series of 1,2-dihydrophosphinine oxides with dialkyl phosphites, diphenylphosphine oxide, and ethyl phenyl-H-phosphinate gave valuable 3-phosphonato-, 3-phosphinoxido-, and 3-phosphinato-1,2,3,6-tetrahydrophosphinine oxides [6][7][8][9], whose twist-boat conformation was stabilized by special intramolecular H-bonds.…”

Section: Introductionmentioning

confidence: 99%

Phospha‐michael reactions involving p‐heterocyclic nucleophiles

Keglevich

Sipos

Takács

et al. 2008

Heteroatom Chemistry

Self Cite

View full text Add to dashboard Cite

P-heterocyclic γ-ketophosphonateswere synthesized by the Michael reaction of methyl vinyl ketone with dibenzo-1,2-oxaphosphorine 2-oxide, 1,3,2-dioxaphosphorine 2-oxide and benzo-1,3,2-dioxaphospholane 2-oxide, respectively. In the first two cases, 50% of 1,8-diazabicyclo[5.4.0]undec-7-ene had to be used that was also required in the addition of dibenzooxaphosphorine oxide to cyclohexenone to result in the formation of the corresponding γ-ketophosphonate. The addition of dibenzooxaphosphorine oxide to less reactive 1,2-dihydrophosphinine oxide was accomplished after activation by an equimolar amount of trimethylaluminum to afford a 3-P(O)<-1,2,3,6-tetrahydrophosphinine oxide, which was subjected to catalytic hydrogenation to provide the corresponding 1,2,3,4,5,6-hexahydrophosphinine oxide.

show abstract

Synthesis of 2‐phosphinoxidomethyl‐ and 2‐phosphonomethyl glutaric acid derivatives

Abstract: Michael addition of the corresponding anions derived from diphenylphosphine oxide, dialkylphosphites, and a cyclic phosphite to α-methylene-glutaric esters (1) afforded the title compounds (2-6). Double debenzylation of 2-phosphono glutaric

Cited by 23 publications

References 7 publications

Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer

Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer

Synthesis of cyclic aminomethylphosphonates and aminomethyl‐arylphosphinic acids by an efficient microwave‐mediated phospha‐mannich approach

Phospha‐michael reactions involving p‐heterocyclic nucleophiles

Contact Info

Product

Resources

About