- M.Sc. Honours School
Dr. Dinesh Mahajan is an experienced medicinal chemist and drug discovery scientist who is pursuing medicinal chemistry and preclinical drug discovery research since last more than 16 years. Dinesh has experience of leading medicinal chemistry department and various drug discovery projects from conception of the idea to delivery of IND (Investigational New Drug) candidate by leading multidiscplinary scientific teams involved in identification/development of chemical hits as well as drug leads by understanding & optimizing Structure Activity relationships (SAR) and ADME-PK properties; late stage pre-clinical evaluation to identify molecules for IND enabling studies. Drug development experience includes, process R&D, new formulations development to address issues like solubility, stability or bio-availability.
At THSTI, his lab and group is focused on drug discovery efforts against NAFLD (Non-alcoholic Fatty Liver Disease) and infecious diseases of national interests such as drug resistant tuberculosis, drug resistant microbial infections and dengue. Most of these discovery effrots are in collaboration with disease biology research groups of the THSTI. In the area of metabolic diseases, his group is also investing efforts in establishing NAFLD disease model in rodents to understand disease pathophyisology as well as to facilitate drug discovery projects.
1. Saroglitazar and Hepano treatment offers protection against high fat high fructose diet induced obesity, insulin resistance and steatosis by modulating various class of hepatic and circulating lipids Soumalya Sarkar, Deepika Kumari, Sonu Kumar Gupta, Vipin Sharma, Sumedha Mukhi, Parul Kamboj, Vedula Sasibhushan, Rajiva Kumar Rai, Sastry Lakshminarayana Jatavallabhula, Dinesh Mahajan, Yashwant Kumar, Ajay Kumar, Madhu Dikshit* Biomedicine & Pharmacotherapy Volume 144, December 2021, 112357.
2. Discovery and Development of SPR519 as a Potent, Selective and Orally Bioavailable Inhibitor of PI3K-alpha and mTOR Kinases for the Treatment of Solid Tumours Dinesh Mahajan* Somdutta Sen, Bilash Kuila, Amit Sharma, Reena Arora, Milind Sagar, Amol Ray Mahapatra, Lalita Babasaheb Gawade and Sundeep Dugar* Journal of Medicinal Chemistry 2020, 63, 19, 11121–11130
3. Synthesis and evaluation of thiophene based small molecules as potent inhibitors of Mycobacterium Tuberculosis (MTB) Chhuttan L. Meena, Padam Singh, Ravi P Shaliwal, Varun Kumar, Arun Kumar, Ramandeep Singh* and Dinesh Mahajan* Eur J Med Chem 2020 15;208:112772.
4. Direct Conversion of Carboxylic Acids to Various Nitrogen Containing Compounds in One-Pot Exploiting Curtius Rearrangement Arun Kumar, Naveen Kumar, Ritika Sharma, Gaurav Bhargava and Dinesh Mahajan* Journal of Organic Chemistry 2019, 84, 17, 11323-11334
5. Catalyst free N-formylation of aromatic and aliphatic amines exploiting reductive formylation of CO 2 using NaBH4 Arun Kumar, Pankaj Sharma, Nidhi Sharma, Yashwant Kumar, Dinesh Mahajan* RSC Adv., 2021, 11, 25777-25787.
6. Recent Advances in the Development of Integrase Inhibitors for HIV Treatment J Trivedi, Dinesh Mahajan, RJ Jaffe, A Acharya, D Mitra, SN Byrareddy Curr HIV/AIDS Rep 2020, 17, 63–75(IF 5.4)
7. Musa balbisiana Fruit Rich in Polyphenols Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats via Inhibition of Inflammation and Oxidative Stress Sima Kumari, Parmeshwar B Katare, R Elancheran, Hina L Nizami, Bugga Paramesha, Sudheer Arava, Partha Pratim Sarma, Roshan Kumar, Dinesh Mahajan, Yashwant Kumar, Rajlakshmi Devi, Sanjay K Banerjee Oxidative Medicine and Cellular Longevity 2020, Article ID 7147498
8. Rhodium-catalysed chemo-and regio-selective [3+ 2+ 2] cycloadditions of bis (methylenecyclopropanes) and alkynes: Synthesis of spirocyclic 5–7 condensed cycloheptenes B Kuila, P Sharma, Dinesh Mahajan, P Singh, G Bhargava Synthetic Communications 2020 50 (6), 840-848
9. Nickel (0)-Catalysed [3+ 2]-Cycloadditions of Bis (alkylidenecyclopropanes) with Diazenes: A Facile Synthesis of Functionalized Pyrazolidine-1, 2-dicarboxylates B Kuila, R Naikoo, Dinesh Mahajan, P Singh, G Bhargava Synlett 2020 31(01) 65-68
10. 11-β-hydroxysterols as possible endogenous stimulators of mitochondrial biogenesis as inferred from epicatechin molecular mimicry S Dugar, F Villarreal, FH Hollinger, Dinesh Mahajan, I Ramirez-Sanchez, Pharmacological research 2020 151, 104540
11. NU-6027 inhibits growth of Mycobacterium tuberculosis by targeting Protein Kinase D and Protein Kinase G Saqib Kidwai, Rania Bouzeyen, Sohini Chakraborti, Neha Khare, Sumana Das, Tannu Priya Gosain, Assirbad Behura, Chhuttan Lal Meena, Rohan Dhiman, Makram Essafi, Avinash Bajaj, Deepak Kumar Saini, Narayanaswamy Srinivasan, Dinesh Mahajan, Ramandeep Singh Antimicrobial Agents and Chemotherapy 2019, DOI: 10.1128/AAC.00996-19.
12. A practically simple, catalyst free and scalable synthesis of N-substituted ureas in water; Lata Tiwari, Varun Kumar, Bhuvesh Kumar and Dinesh Mahajan*; RSC ADV 2018, 8, 21585-21595.
13. Electrophilic activation of carboxylic anhydrides for nucleophilic acylation reactions; Varun Kumar, Anil Rana, Chhuttan Lal Meena, Nidhi Sharma, Yashwant Kumara & Dinesh Mahajan* Synthesis 2018; 50(19): 3902-3910.
14. Triflic anhydride promoted synthesis of primary amides and their conversion to nitriles; Anil Rana, Varun Kumar, Lata Tiwari, Anamika Thakur, Chhuttan Lal Meena, Dinesh Mahajan* SynOpen 20182 (02), 0180-0191.
15. Spermine detection from urine and blood serum using ionic self-assembly of benzimidazolium based dipod and dodecylsulfate; Neetu Tripathia, Prabhpreet Singha, Vijay Luxamib, Dinesh Mahajan, Subodh Kumar Sensors and Actuators B: Chemical 2018, 552-561.
16. Acetylenic Ester Promoted Tandem Ring Opening and Cyclizations of Dienyl Thiazolidin-4-ones: A Facile and Chemoselective Synthesis of Functionalized Pyridine-2-Carboxylates Bilash Kuila, DineshMahajan, Kapil Kumar, Prabhpreet Singh, Gaurav Bhargava; Synlett 2018; 29(04): 509-512.
17. Killing Glioma 'Stem-like' Cells via Drug-Induced Relocation of Endosomal Urokinase Proteins Fredric A Gorin, Nagarekha Pasupuleti, Dinesh Mahajan, Sundeep Dugar; Anti-cancer agents in medicinal chemistry 2017, 40-47.
18. A facile and highly chemoselective synthesis of 1-thia-3a,6-diaza-benzo[e]azulen-3-ones by 7-exo-dig/trig halocyclizations Bilash Kuila, DineshMahajan*, Prabhpreet Singh, Gaurav Bhargava RSC Adv., 2016, 6, 101587.
19. A Facile and chemoselective Synthesis of 1,4-Benzodiazepin-2-ones and Dienyl Thiazolidin-4-ones Bilash Kuila, Yogesh Kumar, DineshMahajan, Prabhpreet Singh, Pankaj, Gaurav Bhargava; RSC Adv., 2016,6, 57485-57489.
20. Discovery of Novel and Orally Bioavailable Inhibitors of PI3 Kinase Based on Indazole Substituted Morpholino-Triazines Sundeep Dugar, Frank P. Hollinger, Dinesh Mahajan*, Somdutta Sen, Bilash Kuila, Reena Arora, Yogesh Pawar, Vaibhav Shinde Mahesh Rahinj, Kamal K. Kapoor, Rahul Bhumkar, Santosh Rai, and Rakesh Kulkarni ACS Med. Chem. Letters 2015 6 (12), pp 1190–1194
21. Synthesis and evaluation of pyrrolotriazine based novel small molecules as selective inhibitors for PI3K kinase Sundeep Dugar, Frank Hollinger, Somdutta Sen, Bilash Kuila and Dinesh Mahajan* Bio. Org. Med Chem Letters 2015, 15, 3142.
22. A concise and efficient synthetic approach to substituted morpholines. Sundeep Dugar, Amit Sharma, Bilash Kuila and Dinesh Mahajan*, Synthesis 2015, 47, 712-720.
23. New small molecules that kill hypoxically transformed glioma stem-like cells Nagarekha Pasupuleti*, Anthony Valenzuela, Yamini Manohar, Dinesh Mahajan, Sundeep Dugar, Jann Sarkaria, Fredric Gorin, Neuro-Ooncology 2015, 17(Supplement5):V31-V31 · NOVEMBER 201.
24. Preclinical activity of dual PI3K/mTOR inhibitor SPR965 in multiple myeloma Jeremy T. Larsen, Vijay Ramakrishnan, Jessica Haug, Teresa Kimlinger, Somdutta Sen, Dinesh Mahajan, Sundeep Dugar, S. Vincent Rajkumar, Shaji K. KumarCancer Research 2015 75(15 Supplement):2653-2653 August 2015; doi: 10.1158/1538-7445.AM2015-2653.
25. SPR965: an oral PI3K/ mTOR C1/C2 inhibitor for the treatment of solid tumors Arora,R.; Dutta, B. K.; Goel, R.; Hollinger, F. P.; Kuila, B.; Mahajan, Dinesh.; Mahapatra, A. R.; Sagar, M.; Sen, S.; Sharma, A.; Dugar, S Cancer Res 2014(Supplement) October 1, 2014 74; 4515;doi: 10.1158/1538-7445.AM2014-4515
26. Nickel catalysed [3+2] cycloaddition reaction of bis(methylenecyclopropane) with cyclic and acyclic dienophiles Bilash Kuila, DineshMahajan, Prabhpreet Singh, Gaurav Bhargava Tetrahedron Letters 2015, 56, 1307-1311
27. Metal-free diastereoselective synthesis of diaza-bicyclo[3.2.0]heptan-7-one and its transformation to functionalized proline esters. Yogesh Kumar, Bilash Kuila, DineshMahajan, Prabhpreet Singh, Balaram Mohapatra, Gaurav Bhargava Tetrahedron Letters2014, 2793-2795.
28. Toward Generic Models of Hemoproteins. Mamadou Lo, Dinesh Mahajan, Jennifer A. Wytko, Corinne Boudon and Jean Weiss, Organic Letters 2009, 2487.
29. Protonated (S)-prolinamide derivatives-water compatible organocatalysts for direct asymmetric aldol reaction S S Chimni, S. Dhami and Dinesh Mahajan Tetrahedron Asymmetry 2008, 2276-2284.
30. Protonated chiral prolinamide catalysed enantioselctive direct aldol reaction in water. S S Chimni, Dinesh Mahajan, V. V. Suresh Babu Tetrahedron Letters 2005, 46, 5617-5619.
31. Small Organic Molecule Catalysed Enantioselective Direct Aldol reaction in Water S S Chimni, Dinesh Mahajan Tetrahedron Asymmetry 2007, 2108-2119.
32. Electron deficiency of the aldehydes controls the pyrrolidine catalysed direct cross aldol reaction of aromatic/heterocyclic aldehydes and ketones in water. S. S. Chimni and Dinesh Mahajan Tetrahedron 2005, 61, 5019-5024.
33. Pyrrolidine catalysed regioselective and diastereoselective direct aldol reaction in water Dinesh Mahajan and S S Chimni, Indian Journal of Chemistry: Sec B Organic and medicinal chemistry 2007, 1355-1358.
Inventor in more than 20 filed patent applications. 18 are published online and 16 are issued or granted patents in different jurisdictions (INDIA, US, China, Europe and Japan).
1. Novel compounds of 11beta-hydroxy-steroids for use in mitochondria biogenesis and diseases associated with mitochondrial dysfunction or depletion, WO/2014/115167; PCT/IN2014/000048; National Phase: China, US, EU and JP.
2. Novel triazine compounds for Pi3K/mTOR pathway, WO2014016849; PCT/IN2013/000458; CN104582707A, EP2874632A4, GrantedUS14/416,140 dated 25/04/2017;Granted JP6175139B2
3. Novel triazine compounds, PCTIN2012000055 Granted US13/981,579 dated 1/11/2016
4. Substituted methylformyl reagents and method of using same to modify physicochemical and/or pharmacokinetic properties of compounds (A new technology patent to address low solubility and bioequivalence of APIs and NCEs), PCTIN2012000248; Granted US14/110,373 dated 07/06/2016; Application pending for grant in China, Europe and Japan
5. Novel compounds, their preparation and their uses, Granted US14/433,485 Dated 31/01/2017 Pending for Grant in China, Europe and Japan (A new technology patent to address low solubility and bioequivalence of APIs and NCEs).
6. Methods of treating tumoral diseases, or bacterial or viral infections, PCT US20170000789; US 15266802 Granted US14/046,682 dated 08/11/2016;AU2013326850A US15/266,802 Pending in Japan, Europe and China
7. A novel process for synthesis of polyphenols (A process patent for non-infringing route of chiral natural product), PCT/IN2012/000052; CN103582635A, EP2668176A2, EP2668176A4, US9428482, Granted US13/981,279 Dated 30/08/2016JP5890846B2 Dated 22/03/2016 EP2668176B1;
8. Novel approach for synthesis of catechins (A process patent for non infringing route for a chiral natural product), PCT/IN2014/000061; CN105026384A, EP2948437A2, EP2948437A4, US9556140, Granted US14/763,018 Dated 31/01/2017; JP6411375B2
9. Flavonoid compounds, PCT/US2012/049767;CN103987704A,EP2739613A4, Granted US14/237,167 dated 17/11/2015
10. Novel compounds, their synthesis and their uses, US09487500
11. Novel compounds and anti-tubercular agents, PCT/IN2015/000226 Granted US15/313,986dated 2018-10-16. Pending in Russia, Europe, China and Japan
12. Novel compounds and inhibition of AKT kinase, IN2014DEL237 20140128
13. Novel analogues of epicatechin and related polyphenols, PCT/IN2014/000213; CN105283179A, EP2981260A2, EP2981260A4, US20160039781; Granted US14/780,214 Dated 22/05/2018
14. Method of converting carbon dioxide into carbonyl compounds WO2019073484 (A1) 12 Dec 2017 Granted in INDIA (A green chemical method of using CO2 gas as a raw material for synthesis of ureas, carbamates and carbonates)
15. Hydroxy Steroid Compounds, their intermediates, process of …US publication number 2015/0376225 A1, Also filed in Europe, China and Japan
16. Novel molecules and their hiv inhibitory activityIndian Pat. Appl. (2018), IN 201711009180 A 20180921.
17. Preparation of trigonelline based compounds as API prodrugs PCT Int. Appl. (2017), WO 2017158621 A1 20170921.
1. Development and PoC validation of a novel approach to treat HIV infection by integrating anti-viral activity with stimulation of host cell innate immunity from DBT-BIRAC under CRS (drug discovery scheme); PI and Project Coordinator; duration May 2017-May 2020 (Completed)
2. Chemical investigation and therapeutic evaluation for linking marker compound(s) with anti-diabetic potential of young shoots of Wendlandia glabrata D.C. and fruits of Phoebe cooperiana, used by indigenous ST people of Arunachal Pradesh.[BT/PR24712/NER/95/828/2017 from DBT- NE Twinning program; 2018-2021. (Completed)
3. Structure determination and targeting of ubiquitously expressed membrane integrated form of chloride intracellular channels (CLICs) for discovery of small molecular anti-cancer therapeutics (BT/PR28766/BRB/10/1701/2018). Duration 3 years till May 2022
4. Penam Laboratories Pvt Ltd, sponsored project for Technology Co-Development (Dec 2018-Oct 2019 Completed).
5. Dabur India Pvt Ltd, sponsored project for development of herbal extracts based formulations for management of NAFLD.
1. Postdoctoral Fellowshipin synthetic organic chemistry by CNRS (2006-07) and MENRT (2007-08) in France.
2. Award for most cited paper 2005-2008-Tetrahedron Letters (Elsevier Ltd. Oxford Press), December 2008
Elsevier Awarded Authors a certificate for Most Citations in Year 2005-2008 for Paper "Protonated chiral prolinamide catalysed enantioselective direct aldol reaction in water"
Tetrahedron Letters 2005, 46, 5617-5619
3. Award for most cited paper 2005-2008-Tetrahedron Asymm. (Elsevier Ltd. Oxford Press), December 2008
Elsevier Awarded Authors a certificate for Most Citations in Year 2005-2008 for Paper "Small Organic Molecule Catalysed Enantioselective Direct Aldol reaction in Water".
Tetrahedron Asymmetry 2007, 2108-2119
4. Senior Research Fellowship(June 2005-july 2006) awarded by University Grant Commission (UGC) of INDIA. This fellowship is awarded by UGC based on research achievements.
5. Award for best oral presentationin National Conference on Modern Trends in Chemical Science and Technology (Oct. 2005).