Eugene Applebaum College of Pharmacy and Health Sciences

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Prof. Aloke K. Dutta   Department of Pharmaceutical Sciences Wayne State University Room   number:     3128 259    Mack     Avenue Detroit,MI 48202                  Email:adutta@wayne.edu Phone: 313-577-1064        Fax: 313-577-2033

Selected Recent Publications (2010-current)

Balaram Ghosh, Tamara Antonio, Juan Zhen, Prashant Kharkar,  Maarten E. A. Reith, Aloke K. Dutta. Development of (S)-N6-Propyl-N6-(2-(4-(quinolin-5-yl)piperazin-1-yl)ethyl)- Development of (S)-N6-(2-(4-(Isoquinolin-1-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor preferring agonist: Potent in vivo activity in Parkinson’s disease animal models. J. Med. Chem. 2010, 53, 1023–1037.

 Balaram Ghosh, Tamara Antonio,,  Maarten E. A. Reith, Aloke K. Dutta.. Discovery of 4-(4-(2-((5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)-ethyl)piperazin-1-yl)quinolin-8-ol and its analogues with dopamine D2/D3 agonists activity with a capacity to bind to iron: potential application in neuroprotective therapy for Parkinson’s Disease. J. Med. Chem. 2010, 53, 2114–2125.

 Chao Li, S. Biswas, Xingang Li, Feifei Luo, A. K. Dutta, Weidong Le. Novel multifunctional drug D-264 for Parkinson’s disease: Evidence of neuroprotective property in PD animal models induced by MPTP and lactacystin. J. Neurosci. Res. 2010, 88, 2513–2523.

 Angela Batman, Aloke Dutta, Patrick Beardsley. Characterising the Behavioural Effects of D-84, a selective DAT inhibitor: Potential as a Replacement Therapy for Cocaine Dependence. Eur. J. Pharmacol. 2010, 648, 127–132. 

Juan Zhen, Tamara Antonio, Aloke K. Dutta, Maarten E.A. Reith. Concentration of receptor and ligand revisited in a modified receptor binding protocol for high-affinity radioligands: [3H]spiperone binding to D2 and D3 dopamine receptors. J. Neurosci. Methods. 2010, 188, 32-38.

 Kyle C Schmitt, Sreeman Mamidyala, Swati Biswas, Aloke K Dutta, Maarten EA Reith. Bivalent Phenethylamines as Novel Dopamine Transporter Inhibitors: Evidence for Multiple Substrate-Binding Sites in a Single Transporter. J. Neurochem. 2010, 112, 1605–1618.

 Balaram Ghosh, Tamara Antonio, Bhaskar Gopishetty, Maarten Reith, Aloke Dutta. Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/ 7-{[2-(4-Aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Bioorg. Med. Chem. 2010, 18, 5661–5674.

 Sandhya Kortagere, Shu-Yuan Cheng, Tamara Antonio, Juan Zhen, Maarten E.A. Reith, Aloke K. Dutta. Interaction of novel hybrid compounds with the D3 dopamine receptor: Site directed mutagenesis and homology modeling studies. Biochem. Pharmacol. 2011, 81, 157–163.

 Sanjib Gogoi, Tamara Antonio, Subramanian Rajagopalan, Maarten Reith, Julie Andersen, Aloke K. Dutta. Dopamine D2/D3 agonist with potent iron chelation, antioxidant and neuroprotective properties: Potential implication in symptomatic and neuroprotective treatment of Parkinson’s disease. ChemMedChem 2011, 6, 991-995.

 Bhaskar Gopishetty, Stuart Hazeldine, Soumava Santra, Mark Johnson, Gyan Modi, Solav Ali, Juan Zhen, Maarten Reith, Aloke Dutta. Further structure activity relationship studies on 4-((((3S,6S)-6-benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol: Identification of compounds with triple uptake inhibitory activity as potential antidepressant agents. J. Med. Chem. 2011, 54, 2924-2932.

 Aloke K. Dutta, Bhaskar Gopishetty, Sanjib Gogoi,  Solav Ali, Juan Zhen, Maarten Reith. The novel trisubstituted pyran derivative D-142 with triple monoamine reuptake inhibitory activity: potent antidepressant-like activity from animal models of depression studies. Eur. J. Pharmacol. 2011, 671, 39–44.

 Bhaskar Gopishetty, Sanjib Gogoi, Aloke Dutta. Development of an efficient asymmetric synthetic route to a novel triple uptake inhibitor antidepressant (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol (D-142). Tetrahedron Asymmetry, 2011, 22, 1081–1086.

 Juan Zhen, Solav Ali, Aloke K. Dutta, Maarten E.A. Reith. Characterization of [H]CFT binding to the norepinephrine transporter suggests that binding of CFT and nisoxetine is not mutually exclusive. J. Neurosci. Methods. 2012, 203(1), 19-27.

 Sanjib Gogoi, Swati Biswas, Antonio Tamara, Maarten Reith, Aloke Dutta. Novel bivalent ligands for D2/D3 dopamine receptors: Significant co-operative gain in D2 affinity and potency. ACS Med. Chem. Lett. 2012, 3(12), 991-996.

Sanjib Gogoi, Soumava Santra, Bhaskar Gopishetty, Tamara Antonio, Juan Zhen,  Maarten Reith, Aloke Dutta. Structural Exploration of (3S,6S)-6-Benzhydryl-N-benzyltetrahydro-2H-pyran-3-amine Analogues: Identification of Potent Triple Monoamine Reuptake Inhibitors as Potential Antidepressants. ChemMedChem, 2012, 7(12), 2093-2100.

Sanjib Gogoi, Asawari Lote, Tamara Antonio, Maarten Reith, Aloke Dutta. D-514, a multifunctional pro-drug with motor stimulating and neuroprotective properties: Possible neuroprotective treatment agent for Parkinson’s disease. Manuscript in preparation.

 Mark Johnson, Tamara Antonio, Maarten Reith, Aloke Dutta. Structure activity relationship study of N6-(2-(4-(1H-indol-5-yl)piperazin-1-yl)ethyl)-N6-propyl-4, 5, 6, 7-tetrahydrobenzo[d]thiazole-2, 6-diamine analogues: Development of highly selective D3 dopamine receptor agonists along with highly potent D2/D3 agonist and their pharmacological characterization. J. Med. Chem. 2012, 55, 5826-5840.

 Eldo Kuzhikandathil, Samantha Cote, Soumava Santra, Aloke K. Dutta. Interaction of D3 preferring agonist (─)-N6-(2-(4-(Biphenyl-4-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264) with cloned human D2L, D2S and D3 receptors: Potent stimulation of mitogen-activated protein kinases and G-protein coupled inward rectifier potassium channels. Naunyn-Schmiedeberg's Archives of Pharmacology, 2013, 386(2), 97-105. 

Soumava Santra, Liping Xu, Mrudang Shah, Mark Johnson, Aloke Dutta. D-512 and D-440 as novel multifunctional dopamine agonists: Characterization of neuroprotection properties and evaluation of in vivo efficacy in a Parkinson’s disease animal model. ACS Chem. Neurosci. 2013, 4(10), 1382–1392.

 Soumava Santra, Liping Xu, Mark Johnson, Sanjib Gogoi, Tamara Antonio, Maarten E. A. Reith, Aloke K. Dutta.  (2013) Approach towards development of multifunctional drugs as an effective strategy for treatment of Parkinson’s disease. In L. Eiden (Ed.), Catecholamine Research in the 21st Century: Abstracts and Graphical Abstracts, 10th International Catecholamine Symposium 2012, 148-149, Oxford, UK: Elsevier.

Bhaskar Gopishetty, Suhong Zhang, Prashant S. Kharkar, Tamara Antonio, Maarten Reith, Aloke K. Dutta. Modification of agonist binding moiety in hybrid derivative 5/ 7-{[2-(4-Aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/ -2-amino versions: Impact on functional activity and selectivity for dopamine D2/D3 receptors. Bioorg. Med. Chem. 2013, 21, 3164–3174.

Gyan Modi, Tamara Antonio, Maarten Reith, Aloke Dutta. Structural Modifications of Neuroprotective Anti-Parkinsonian (−)N6(2-(4-(Biphenyl-4-yl)piperazin-1-yl)-ethyl)N6propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264): An Effort toward the Improvement of in Vivo Efficacy of the Parent Molecule. J. Med. Chem. 2014, 57, 1557−1572.

Mrudang Shah, Chandrasekhar Voshavar, Liping Xu, Subramanian Rajagopalan, Julie Andersen, Aloke Dutta. High affinity D2/D3 agonist D512 protects PC12 cells from 6-OHDA induced apoptotic cell death and rescued dopaminergic neurons in the MPTP mouse model of Parkinson’s disease. J. Neurochem. 2014, 131, 74–85.

Horrick Sharma, Soumava Santra, Joy Debnath, Bhaskar Gopishetty, Tamara Antonio, Maarten Reith, Aloke Dutta. Flexible and biomimetic analogs of triple uptake inhibitor 4-((((3S,6S)-6-benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol : Synthesis, biological characterization, and development of a pharmacophore model. Bioorg. Med. Chem. 2014, 22, 311–324.

Gyan Modi, Chandrashekhar Voshavar, Mrudang Shah, Tamara Antonio, Maarten Reith, Aloke Dutta. Multifunctional D2/D3 agonist D-520 with high in vivo efficacy: Modulator of toxicity of Alpha synuclein aggregates. ACS Chem. Neurosci. 2014, 5, 700–717.

Gyan Modi, Horrick Sharma, Prashant S. Kharkar, Aloke Dutta. Understanding the structural requirements of hybrid (S)-6-((2-(4-phenylpiperazin-1-yl)ethyl)(propyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol and its analogs as D2/D3 receptor ligands. A three-dimensional quantitative structure-activity relationship (3D QSAR) investigation. Medchemcomm. 2014, 5(9), 1384-1399.

Aloke Dutta, Soumava Santra, Horrick Sharma, Chandrasekhar Voshavar, Liping Xu, Omar Mabrouk, Tamara Antonio, Maarten Reith. Pharmacological and behavioral characterization of an orally active triple reuptake inhibitor D-473: Effects of drug on extracellular levels of dopamine, serotonin and norepinephrine. PLoS One, 2014, 9, e113420.

Soumava Santra, Horrick Sharma, Seenuvasan Vedachalam, Tamara Antonio, Maarten Reith, Aloke Dutta. Development of potent dopamine-norepinephrine uptake inhibitors (DNRIs) based on (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl) amino)tetrahydro-2H-pyran-4-ol molecular template. Bioorg. Med. Chem. 2015, 23, 821-828.

Banibrata Das, Gyan P. Modi, Aloke K. Dutta. Dopamine D3 agonists in the Treatment of Parkinson's Disease. Curr. Top. Med. Chem., 2015, 15(10), 908-926.

Juan Zhen, Tamara Antonio, Solav Ali, Kim A. Neve, Aloke K. Dutta, Maarten E.A. Reith. Use of radiolabeled antagonist assays for assessing agonism at D2 and D3 dopamine receptors: Comparison with functional GTPγs assays. J. Neurosci. Methods. 2015, 248, 7-15.

Chandrasekhar Voshavar, Mrudang Shah, Liping Xu, Aloke Dutta. Assessment of protective role of multifunctional dopamine agonist D-512 against Oxidative stress produced by depletion of Glutathione in PC12 cells: Implication in neuroprotective therapy for Parkinson’s disease. Neurotoxicity Research, 2015, 1-17.

Soumava Santra, Horrick Sharma, Aloke Dutta. Triple Uptake Inhibitor as a potential new generation antidepressant agents. Future Med. Chem. 2015, 7(17)2385-2406.

Banibrata Das, Seenuvasan Vedachalam, Dan Luo, Tamara Antonio, Maarten Reith, Aloke Dutta. Development of a highly potent D2/D3 agonist and a partial agonist from structure-activity relationship study of N(6)-(2-4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine analogues: Implication in the treatment of Parkinson's disease. J. Med. Chem. 2015, 58(23), 9179-9195.

Juan Zhen, Tamara Antonio, Aloke K. Dutta, Dana Salley, Maarten E.A. Reith. Efficacy of hybrid tetrahydrobenzo[d]thiazole based aryl piperazines D-264 and D-301 at D2 and D3 receptors. Neurochemical Research, 2016, 41(1-2), 328-39.

Fahd Dholkawala, Chandrashekhar Voshavar, Aloke K. Dutta. Synthesis and characterization of brain penetrant prodrug of neuroprotective D-264: Potential therapeutic application in the treatment of Parkinson’s disease. J. Pharmaceutics and Biopharmaceutics, 2016, 103, 62–70.

Deepthi Yedlapudi, Gnanada Joshi, Dan Luo, Sokol Todi, Aloke K. Dutta. Inhibition of alpha-synuclein aggregation by multifunctional dopamine agonists assessed by a novel in vitro assay and an in vivo Drosophila synucleinopathy model. Scientific Reports 6, Article number: 38510 (2016).  doi:10.1038/srep38510. 

Dan Luo, Horrick Sharma, Deepthi Yedlapudi, Tamara Antonio, Maarten E.A. Reith, Aloke K. Dutta. Novel multifunctional dopamine D2/D3 receptors agonists as modulator of aggregation of alpha synuclein protein with potential neuroprotective property. Bioorganic & Medicinal Chemistry, 2016, 24, 5088–5102.

Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy Stemmler, Maarten Reith, Aloke Dutta. A novel iron(II) preferring dopamine agonist chelator as potential symptomatic and neuroprotective therapeutic agent for Parkinson's disease. ACS Chem. Neurosci. 2017, 8, 723-730.

Banibrata Das, Subramanian Rajagopalan, Gnanada S. Joshi, Liping Xu, Dan Luo, Julie K. Andersen, Sokol V. Todi, Aloke K. Dutta. A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo. Neuropharmacology. 2017, 123, 88-99.

 

APPROVED PATENTS

 1. N- AND O-SUBSTITUTED 4-[2-(DIPHENYLMETHOXY)-ETHYL]-1-(PHENYL) METHYL) PIPERIDINE ANALOGS AND METHODS OF TREATING CNS DISORDERS THEREWITH. PATENT NO: US 6,995,268 B2; FEBRUARY 7 2006.

 2. HYBRID 2-AMINOTETRALIN AND ARYL-SUBSTITUTED PIPERAZINE COMPOUNDS AND THEIR USE IN ALTERING CNS ACTIVITY. PATENT NO: US 6,982,332, JANUARY 3, 2006.

 3. Derivatives of 2-aminotetralins and pharmaceutical analogs thereof exhibiting differentail cns receptor activity and behavior. Patent NO: US 7049337 B2; May 23, 2006.

 4. N-AND O-SUBSTITUTED 4-[2-( DIPHENYLMETHOXY) -ETHYL]-1- (PHENYL) METHYL) PIPERIDINE ANALOGS AND METHODS OF TREATING CNS DISORDERS THEREWITH. U.S. Pat. No. 7,595,331, September 29, 2009.

 5. HYBRID 2-AMINOTETRALIN AND ARYL-SUBSTITUTED PIPERAZINE COMPOUNDS AND THEIR USE IN ALTERING CNS ACTIVITY . U.S. Patent Appn. No. 11/235612 (WSU 0197 PUSA1). Status:  Patented as U.S. Pat. No. 7,723,519.  Issue Date:  May 25, 2010.

 6. Dutta, A. K. “Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives.”, WSU 0203PUSA, U.S. Pat. No. US7,915,433 B2, March 29, 2011.

 7. Dutta, A. K. “Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives.”, WSU 0203PUSA, U.S. Pat. No. US8,017,791, September 13, 2011.

 8. HYBRID 2-AMINOTETRALIN AND ARYL-SUBSTITUTED PIPERAZINE COMPOUNDS AND THEIR USE IN ALTERING CNS ACTIVITY. PATENT NO: US 8,227,604 B2, July 24, 2012.

 9. Dutta, A. K. “Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives.”, WSU 0203PUSA, U.S. Pat. No. US8,519,159 B2, August 27, 2013.

 10. Dutta, A. K. “TRI-SUBSTITUTED 2-BENZHYDRYL-5-BENZLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OL ANALOGUES, AND NOVEL 3,6-DISUBSTITUTED PYRAN DERIVATIVES”. European Pat. No. EP 1 976 381 B1, July 24, 2013.

 11. Dutta, A. K. “TRI-SUBSTITUTED 2-BENZHYDRYL-5-BENZLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OL ANALOGUES, AND NOVEL 3,6-DISUBSTITUTED PYRAN DERIVATIVES”. European Pat. No. EP 1 734948 B1, June 11, 2014.

 12. Dutta, A. K. Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives. U.S. Pat. No. US 8,841,464, September 23, 2014.

 FILED PATENTS

 1. A novel hybrid series of compounds derived from 2-aminotetralin and piperazine based derivatives: characterization for D1, D2, D3, D4 and serotoninergic receptor subtypes binding  U.S. Patent Appn. No. 12/770,079 (WSU 0197 PUSA2). Status:  Pending, no action yet. Filing Date:  April 29, 2010.

 2. WSU 0210 Patent Family. Title:  BIFUNCTIONAL/POLYFUNCTIONAL DOPAMINE D2/D3 AGONIST AS NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES, WSU 0210 PCT, PCT/US2010/031900, April 2010.

 

 

 

 

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Last Updated 03/18/2017. Designed by Dr. Soumava Santra/Dr. Banibrata Das and Maintained by Prof. Aloke K. Dutta