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Sreeni Labs Private Limited, Hyderabad, India ready to deliver New, Economical, Scalable Routes to your advanced intermediates & API’s in early Clinical Drug Development Stages
Sreeni Labs Private Limited, Hyderabad, India is ready to take up challenging synthesis projects from your preclinical and clinical development and supply from few grams to multi-kilo quantities. Sreeni Labs has proven route scouting ability to design and develop innovative, cost effective, scalable routes by using readily available and inexpensive starting materials. The selected route will be further developed into a robust process and demonstrate on kilo gram scale and produce 100’s of kilos of in a relatively short time.
Accelerate your early development at competitive price by taking your route selection, process development and material supply challenges (gram scale to kilogram scale) to Sreeni Labs…………
Sreeni Labs based in Hyderabad, India is working with various global customers and solving variety of challenging synthesis problems. Their customer base ranges from USA, Canada, India and Europe. Sreeni labs Managing Director, Dr. Sreenivasa Reddy Mundla has worked at Procter & Gamble Pharmaceuticals and Eli Lilly based in USA.
The main strength of Sreeni Labs is in the design, development of innovative and highly economical synthetic routes and development of a selected route into a robust process followed by production of quality product from 100 grams to 100s of kg scale. Sreeni Labs main motto is adding value in everything they do.
They have helped number of customers from virtual biotech, big pharma, specialty chemicals, catalog companies, and academic researchers and drug developers, solar energy researchers at universities and institutions by successfully developing highly economical and simple chemistry routes to number of products that were made either by very lengthy synthetic routes or by using highly dangerous reagents and Suzuki coupling steps. They are able to supply materials from gram scale to multi kilo scale in a relatively short time by developing very short and efficient synthetic routes to a number of advanced intermediates, specialty chemicals, APIs and reference compounds. They also helped customers by drastically reducing number of steps, telescoping few steps into a single pot. For some projects, Sreeni Labs was able to develop simple chemistry and avoided use of palladium & expensive ligands. They always begin the project with end in the mind and design simple chemistry and also use readily available or easy to prepare starting materials in their design of synthetic routes
Over the years, Sreeni labs has successfully made a variety of products ranging from few mg to several kilogram scale. Sreeni labs has plenty of experience in making small select libraries of compounds, carbocyclic compounds like complex terpenoids, retinal derivatives, alkaloids, and heterocyclic compounds like multi substituted beta carbolines, pyridines, quinolines, quinolones, imidazoles, aminoimidazoles, quinoxalines, indoles, benzimidazoles, thiazoles, oxazoles, isoxazoles, carbazoles, benzothiazoles, azapines, benzazpines, natural and unnatural aminoacids, tetrapeptides, substituted oligomers of thiophenes and fused thiophenes, RAFT reagents, isocyanates, variety of ligands, heteroaryl, biaryl, triaryl compounds, process impurities and metabolites.
Sreeni Labs is Looking for any potential opportunities where people need development of cost effective scalable routes followed by quick scale up to produce quality products in the pharmaceutical & specialty chemicals area. They can also take up custom synthesis and scale up of medchem analogues and building blocks. They have flexible business model that will be in sink with customers. One can test their abilities & capabilities by giving couple of PO based (fee for service) projects.
Some of the compounds prepared by Sreeni labs;
See presentation below
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Managing Director at Sreeni Labs Private Limited\
Few Case Studies : Source SEEENI LABS
One virtual biotech company customer from USA, through a common friend approached Sreeni Labs and told that they are buying a tetrapeptide from Bachem on mg scale at a very high price and requested us to see if we can make 5g. We accepted the challenge and developed solution phase chemistry and delivered 6g and also the process procedures in 10 weeks time. The customer told that they are using same procedures with very minor modifications and produced the tetrapeptide ip to 100kg scale as the molecule is in Phase III.
One East coast customer in our first meeting told that they are working with 4 CROs of which two are in India and two are in China and politely asked why they should work with Sreeni Labs. We told that give us a project where your CROs failed to deliver and we will give a quote and work on it. You pay us only if we deliver and you satisfy with the data. They immediately gave us a project to make 1.5g and we delivered 2g product in 9 weeks. After receiving product and the data, the customer was extremely happy as their previous CRO couldn’t deliver even a milligram in four months with 3 FTEs.
One Midwest biotech company was struggling to remove palladium from final API as they were doing a Suzuki coupling with a very expensive aryl pinacol borane and bromo pyridine derivative with an expensive ligand and relatively large amount of palldium acetate. The cost of final step catalyst, ligand and the palladium scavenging resin were making the project not viable even though the product is generating excellent data in the clinic. At this point we signed an FTE agreement with them and in four months time, we were able to design and develop a non suzuki route based on acid base chemistry and made 15g of API and compared the analytical data and purity with the Suzuki route API. This solved all three problems and the customer was very pleased with the outcome.
One big pharma customer from east coast, wrote a structure of chemical intermediate on a paper napkin in our first meeting and asked us to see if we can make it. We told that we can make it and in less than 3 weeks time we made a gram sample and shared the analytical data. The customer was very pleased and asked us to make 500g. We delivered in 4 weeks and in the next three months we supplied 25kg of the same product.
Through a common friend reference, a European customer from a an academic institute, sent us an email requesting us to quote for 20mg of a compound with compound number mentioned in J. med. chem. paper. It is a polycyclic compound with four contiguous stereogenic centers. We gave a quote and delivered 35 mg of product with full analytical data which was more pure than the published in literature. Later on we made 8g and 6g of the same product.
One West coast customer approached us through a common friend’s reference and told that they need to improve the chemistry of an advanced intermediate for their next campaign. At that time they are planning to make 15kg of that intermediate and purchased 50kg of starting raw material for $250,000. They also put five FTEs at a CRO for 5 months to optimize the remaining 5 steps wherein they are using LAH, Sodium azide, palladium catalyst and a column chromatography. We requested the customer not to purchase the 50kg raw material, and offered that we will make the 15kg for the price of raw material through a new route in less than three months time. You pay us only after we deliver 15 kg material. The customer didn’t want to take a chance with their timeline as they didn’t work with us before but requested us to develop the chemistry. In 7 weeks time, we developed a very simple four step route for their advanced intermediate and made 50g. We used very inexpensive and readily available starting material. Our route gave three solid intermediates and completely eliminated chromatographic purifications.
One of my former colleague introduced an academic group in midwest and brought us a medchem project requiring synthesis of 65 challenging polyene compounds on 100mg scale. We designed synthetic routes and successfully prepared 60 compounds in a 15 month time.
The man behind Seeni labs is Dr. Sreenivasa Reddy Mundla
Dr. Sreenivasa Reddy Mundla.
Managing Director at Sreeni Labs Private Limited
Sreeni Labs Private Limited
Road No:12, Plot No:24,25,26
- IDA, Nacharam
Telangana State, India
Dr. Sreenivasa Reddy Mundla
Dr. M. Sreenivasa Reddy obtained Ph.D from University of Hyderabad under the direction Prof Professor Goverdhan Mehta in 1992. From 1992-1994, he was a post doctoral fellow at University of Wisconsin in Professor Jame Cook’s lab. From 1994 to 2000, worked at Chemical process R&D at Procter & Gamble Pharmaceuticals (P&G). From 2001 to 2007 worked at Global Chemical Process R&D at Eli Lilly and Company in Indianapolis.
In 2007 resigned to his job and founded Sreeni Labs based in Hyderabad, Telangana, India and started working with various global customers and solving various challenging synthesis problems.
The main strength of Sreeni Labs is in the design, development of a novel chemical route and its development into a robust process followed by production of quality product from 100 grams to 100’s of kg scale.
They have helped number of customers by successfully developing highly economical simple chemistry routes to number of products that were made by Suzuki coupling. they are able to shorten the route by drastically reducing number of steps, avoiding use of palladium & expensive ligands. they always use readily available or easy to prepare starting materials in their design of synthetic routes.
Sreeni Labs is Looking for any potential opportunities where people need development of cost effective scalable routes followed by quick scale up to produce quality products in the pharmaceutical & specialty chemicals area. They have flexible business model that will be in sink with customers. One can test their abilities & capabilities by giving PO based projects
August 2007 – Present (8 years 11 months)
March 2001 – August 2007 (6 years 6 months)
July 1994 – February 2001 (6 years 8 months)
Aug 2010 · ChemInform
Article: Optimization of a Dihydropyrrolopyrazole Series of Transforming Growth Factor-β Type I Receptor Kinase Domain Inhibitors: Discovery of an Orally Bioavailable Transforming Growth Factor-β Receptor Type I Inhibitor as Antitumor Agent
Hong-yu Li · William T. McMillen · Charles R. Heap · Denis J. McCann · Lei Yan · Robert M. Campbell · Sreenivasa R. Mundla · Chi-Hsin R. King · Elizabeth A. Dierks · Bryan D. Anderson · Karen S. Britt · Karen L. Huss
Apr 2008 · Journal of Medicinal Chemistry
Feb 2008 · ChemInform
Nov 2007 · Tetrahedron
Article: Dihydropyrrolopyrazole Transforming Growth Factor-β Type I Receptor Kinase Domain Inhibitors: A Novel Benzimidazole Series with Selectivity versus Transforming Growth Factor-β Type II Receptor Kinase and Mixed Lineage Kinase-7
Hong-yu Li · Yan Wang · Charles R Heap · Chi-Hsin R King · Sreenivasa R Mundla · Matthew Voss · David K Clawson · Lei Yan · Robert M Campbell · Bryan D Anderson · Jill R Wagner ·Karen Britt · Ku X Lu · William T McMillen · Jonathan M Yingling
Apr 2006 · Journal of Medicinal Chemistry
Aug 2003 · Tetrahedron Letters
Nov 2000 · ChemInform
Nov 2000 · ChemInformAug 2000 · Tetrahedron LettersAug 2000 · Tetrahedron LettersArticle: Synthesis and Evaluation of Analogues of the Partial Agonist 6-(Propyloxy)-4-(methoxymethyl)-β-carboline-3-carboxylic Acid Ethyl Ester (6-PBC) and the Full Agonist 6-(Benzyloxy)-4-(methoxymethyl)-β- carboline-3-carboxylic Acid Ethyl Ester (Zk 93423) at Wild Type and Recombinant GABA A Receptors
The present invention provides 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl) -5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate, i.e., Formula I.
EXAMPLE 1 Preparation of 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl-5,6-dihydro-4H -pyrrolo[1,2-b]pyrazole monohydrate
1H NMR (CDCl3): δ=9.0 ppm (d, 4.4 Hz, 1H); 8.23-8.19 ppm (m, 2H); 8.315 ppm (dd, 1.9 Hz, 8.9 Hz, 1H); 7.455 ppm (d, 4.4 Hz, 1H); 7.364 ppm (t, 7.7 Hz, 1H); 7.086 ppm (d, 8.0 Hz, 1H); 6.969 ppm (d, 7.7 Hz, 1H); 6.022 ppm (m, 1H); 5.497 ppm (m, 1H); 4.419 ppm (t, 7.3 Hz, 2H); 2.999 ppm (m, 2H); 2.770 ppm (p, 7.2 Hz, 7.4 Hz, 2H); 2.306 ppm (s, 3H); 1.817 ppm (m, 2H). MS ES+: 370.2; Exact: 369.16
ABOVE MOLECULE IS
A TGF-beta receptor type-1 inhibitor potentially for the treatment of myelodysplastic syndrome (MDS) and solid tumours.
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KEYWORDS Sreenivasa Mundla Reddy, Managing Director, Sreeni Labs Private Limited, Hyderabad, Telangana, India, new, economical, scalable routes, early clinical drug development stages, Custom synthesis, custom manufacturing, drug discovery, PHASE 1, PHASE 2, PHASE 3, API, drugs, medicines
PHASE 1 CHINA
PRoject Name: HAO472 treatment Phase I clinical trial in relapsed / refractory AML, M2b type of AML
The main purpose: to determine HAO472 treatment of relapsed / refractory C the maximum tolerated dose (MTD). Secondary objectives: 1) evaluation of drug safety and tolerability; 2) study HAO472 in pharmacokinetic characteristics of the human body; 3) the effectiveness of HAO472 treatment of relapsed / refractory M2b type of AML.
Acute myelogenous leukemia
Test Number: CTR20150246
Jiangsu Hengrui Medicine Co., Ltd. 1/
2 Ruijin Hospital, Shanghai Jiaotong University School of Medicine /
3 Jiangsu Hengrui Medicine Co., Ltd. /
4 Shanghai Hengrui Medicine Co., Ltd. /
Natural products have historically been, and continue to be, an invaluable source for the discovery of various therapeutic agents. Oridonin, a natural diterpenoid widely applied in traditional Chinese medicines, exhibits a broad range of biological effects including anticancer and anti-inflammatory activities. To further improve its potency, aqueous solubility and bioavailability, the oridonin template serves as an exciting platform for drug discovery to yield better candidates with unique targets and enhanced drug properties. A number of oridonin derivatives (e.g. HAO472) have been designed and synthesized, and have contributed to substantial progress in the identification of new agents and relevant molecular mechanistic studies toward the treatment of human cancers and other diseases. This review summarizes the recent advances in medicinal chemistry on the explorations of novel oridonin analogues as potential anticancer therapeutics, and provides a detailed discussion of future directions for the development and progression of this class of molecules into the clinic.
Oridonin displays significant anticancer activities via multi-signaling pathways.
Recent advances in medicinal chemistry of oridonin-like compounds are presented.
The article summarizes the SAR and mechanism studies of relevant drug candidates.
The milestones and future direction of oridonin-based drug discovery are discussed.
Discovery and development of natural product oridonin-inspired anticancer agents
- a Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States
- b Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States
////////Natural product, Oridonin, Diterpenoids, Anticancer agents, Drug discovery, Chemical biology, AML, HAO 472, relapsed / refractory AML. Jiangsu Hengrui Medicine Co., Ltd, PHASE1, LEUKEMIA
Figure 2. a. Fragment-based screening: Small and structurally diverse molecules (circles represent functional groups) are screened for a biological target, and they are combined and modified to generate drug-like compounds. b. Diversity-oriented synthesis: Large collections of structurally diverse and complex molecules are made using a short number of reactions. The resulting compounds are optimized to produce the drug-like compounds. | Credit: P. J. Hajduk,W. R. J. D. Galloway & D. R. Spring Nature, 2011, 470, 42–43. DOI: 10.1038/470042a
The discovery and development of new drugs is a long and expensive process, and despite of it, essential to face present and new diseases. For small molecules, which account for the majority of the marketed drugs, the discovery process generally involves finding a starting point termed hit or lead compound. These molecules have biological activity but need to be optimized to enhance their potency and selectivity (i.e. minimize the toxicity) and improve pharmacokinetic parameters making them suitable to go to the next stage, the pre-clinical tests……….http://mappingignorance.org/2014/07/04/lead-oriented-synthesis-new-concept-aid-drug-discovery-process/
Piramal Drops Drug Discovery,…………. Pharmaceuticals: Risks and regulations convince the Indian company to reallocate resources
In a move that raises questions about the future of drug research in India, Piramal Enterprises will end its drug discovery activities. The decision—which involves possible job losses—will affect several hundred scientists, many of whom were recruited internationally to work in Mumbai in one of India’s most sophisticated pharmaceutical labs.
The company has been considered an Indian leader in drug research since opening its discovery labs in 2004. Within the firm, drug discovery was championed by the vice chairman, Swati A. Piramal, a medical doctor who also holds a master’s degree from the Harvard School of Public Health.
“After reevaluating the risk-benefits of new chemical entity research, the company decided to focus resources on our other areas of R&D with shorter development timelines and different risk profiles,” Piramal tells C&EN.
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Piramal Enterprises, which sold off its domestic formulations business to Abbott in a multi-billion dollar deal a few years ago, is now shutting down its Mumbai-based R&D unit which would in effect bring to an end its early stage drug discovery business.
Separate media reports, citing Swati Piramal, part of the promoter group of the diversified firm and wife of group chief Ajay Piramal, said, the decision to move away from the drug discovery business was taken given the costs of basic research.
The company would now focus on molecules at an advanced stage of development; resources would be redeployed from basic research to the clinical unit.
Its other research facilities are located in Chennai, Hyderabad, Ahmedabad and Indore, which would continue to be functional.
Although Piramal Enterprises retains its exposure to healthcare as a sector, after selling the key pharma business, it is now more associated with financial services, including investments in infrastructure and real estate sectors.
In an unrelated development, the firm is forming a joint venture with Navin Fluorine International Limited, an Arvind Mafatlal Group company, to develop, manufacture and sell specialty fluorochemicals with a focus on applications in healthcare, according to a company release.
As per the agreement, Piramal Enterprises will hold 51 per cent of the equity share capital of the proposed joint venture company, whereas the remaining 49 per cent will be held by Navin.
In the first phase of development, the JV is expected to invest around Rs 120 crore in India for this project.
Mumbai-based Navin Fluorine has a turnover of around $100 million. It specialises in specialty fluorine. It had acquired UK-based Manchester Organics, a specialty fluorochemicals research company in 2011.
chemical transformations. Its applications are increasingly found in all aspects of drug
discovery, ranging from lead finding through combinatorial chemistry and target-templated …
and reliable chemical transformations. Its applications are increasingly
found in all aspects of drug discovery, ranging from lead finding through
combinatorial chemistry and target-templated in situchemistry, to proteomics
and DNA research, using bioconjugation reactions. The copper-(I)-catalyzed
1,2,3-triazole formation from azides and terminal acetylenes is a particularly
powerful linking reaction, due to its high degree of dependability, complete
specificity, and the bio-compatibility of the reactants. The triazole products
are more than just passive linkers; they readily associate with biological
targets, through hydrogen bonding and dipole interactions.
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The use of drug-like macrocycles is emerging as an exciting area of medicinal chemistry, with several recent examples highlighting the favorable changes in biological and physicochemical properties that macrocyclization can afford. Natural product macrocycles and their synthetic derivatives have long been clinically useful and attention is now being focused on the wider use of macrocyclic scaffolds in medicinal chemistry in the search for new drugs for increasingly challenging targets. With the increasing awareness of concepts of drug-likeness and the dangers of ‘molecular obesity’, functionalized macrocyclic scaffolds could provide a way to generate ligand-efficient molecules with enhanced properties. In this review we will separately discuss the effects of macrocyclization upon potency, selectivity and physicochemical properties, concentrating on recent case histories in oncology drug discovery. Additionally, we will highlight selected advances in the synthesis of macrocycles and provide an outlook on the future use of macrocyclic scaffolds in medicinal chemistry.
The field of biotechnology has revolutionized the drug discovery process. Recombinant DNA-driven drug discovery process is beginning to add new avenues for some old drugs. In its infancy, genetic engineering was considered useful only for the production of therapeutic proteins. Insulin, for example, previously prepared by isolation of pancreatic tissue of bovine or porcine species, can now be prepared identical to human insulin by biotechnology. Companies like Genentech and Biogen were founded solely with this objective. However, proteins do not make ideal drugs, being difficult to administer, rapidly cleared, and potentially immunogenic. Despite these disadvantages, a rapidly increasing number of “biopharmaceuticals” including recombinant proteins, therapeutic monoclonal antibodies, and even antisense oligonucleosides have been approved for indications ranging from metastatic breast cancer (Herceptin) to rheumatoid arthritis (Remicade, Enbrel).
|Giridhar R. Drug discovery: Past and present. J Adv Pharm Technol Res 2012;3:2|
|Giridhar R. Drug discovery: Past and present. J Adv Pharm Technol Res [serial online] 2012 [cited 2014 Aug 15];3:2. Available from: http://www.japtr.org/text.asp?2012/3/1/2/93554|
To start with the simplest one is Quantitative structure-activity relationship (QSAR) which is also referred to as 2D-QSAR sometimes. 3D-QSAR involving Comparative Molecular Field Analysis (CoMFA) and Comparative molecular similarity index analysis (CoMSIA) are extension of QSAR. QSAR is not able to take the three dimensional structure of a molecule into consideration due to absence of three-dimensional parameterization of structures. 3D-QSAR scores over QSAR in this respect. Docking studies throw more light on the binding modes of drugs with their target proteins but it is feasible only when the crystal structure of the target enzyme/protein is known with good resolution. Docking studies are also used for virtual screening of databases. But the ideal technique for virtual screening of compounds is through pharmacophore mapping and screening, especially when the structure of the target is not known. Very large databases can be first screened by pharmacophorebecause the technique is quite fast followed by screening of the positive hits using docking studies. Insilico designing of novel compounds can also be performed using deNovodesigning techniques subject to the condition that the target structure in known.
|Yadav M R. New drug discovery: Where are we heading to?. J Adv Pharm Technol Res 2013;4:2-3|
Yadav M R. New drug discovery: Where are we heading to?. J Adv Pharm Technol Res [serial online] 2013 [cited 2014 Aug 12];4:2-3. Available from: http://www.japtr.org/text.asp?2013/4/1/2/107493