Publications by authors named "Damoder Reddy Motati"

7 Publications

  • Page 1 of 1

Azaindole therapeutic agents.

Bioorg Med Chem 2020 12 30;28(24):115830. Epub 2020 Oct 30.

Department of Pharmacology and Chemical Biology, Emory University School of Medicine, 1510 Clifton Rd, Atlanta, GA 30322, United States. Electronic address:

Azaindole structural framework is an integral part of several biologically active natural and synthetic organic molecules; and several FDA approved drugs for various diseases. In the last decade, quite a number of literature reports appeared describing the pharmacology, biological activity and therapeutic applications of a variety of azaindole molecules. This prompted the organic and medicinal chemistry community to develop novel synthetic methods for various azaindoles and test them for a bioactivity against a variety of biological targets. Herein, we have summarized the biological activity of therapeutically advanced clinical candidates and several preclinical candidate drugs that contain azaindole structural moiety.
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http://dx.doi.org/10.1016/j.bmc.2020.115830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736151PMC
December 2020

Potent, Selective, Water Soluble, Brain-Permeable EP2 Receptor Antagonist for Use in Central Nervous System Disease Models.

J Med Chem 2020 02 16;63(3):1032-1050. Epub 2020 Jan 16.

Department of Pharmacology and Chemical Biology , Emory University School of Medicine , 1510 Clifton Rd , Atlanta , Georgia 30322 , United States.

Activation of prostanoid EP2 receptor exacerbates neuroinflammatory and neurodegenerative pathology in central nervous system diseases such as epilepsy, Alzheimer's disease, and cerebral aneurysms. A selective and brain-permeable EP2 antagonist will be useful to attenuate the inflammatory consequences of EP2 activation and to reduce the severity of these chronic diseases. We recently developed a brain-permeable EP2 antagonist (TG6-10-1), which displayed anti-inflammatory and neuroprotective actions in rodent models of status epilepticus. However, this compound exhibited moderate selectivity to EP2, a short plasma half-life in rodents (1.7 h) and low aqueous solubility (27 μM), limiting its use in animal models of chronic disease. With lead-optimization studies, we have developed several novel EP2 antagonists with improved water solubility, brain penetration, high EP2 potency, and selectivity. These novel inhibitors suppress inflammatory gene expression induced by EP2 receptor activation in a microglial cell line, reinforcing the use of EP2 antagonists as anti-inflammatory agents.
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http://dx.doi.org/10.1021/acs.jmedchem.9b01218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394479PMC
February 2020

The Discovery and Development of Oxalamide and Pyrrole Small Molecule Inhibitors of gp120 and HIV Entry - A Review.

Curr Top Med Chem 2019 ;19(18):1650-1675

Department of Pharmaceutical Sciences, Center for Pharmacometrics and Molecular Discovery, College of Pharmacy, Union University, Jackson, Tennessee 38305, United States.

Human immunodeficiency virus type-1 (HIV-1) is the causative agent responsible for the acquired immunodeficiency syndrome (AIDS) pandemic. More than 60 million infections and 25 million deaths have occurred since AIDS was first identified in the early 1980s. Advances in available therapeutics, in particular combination antiretroviral therapy, have significantly improved the treatment of HIV infection and have facilitated the shift from high mortality and morbidity to that of a manageable chronic disease. Unfortunately, none of the currently available drugs are curative of HIV. To deal with the rapid emergence of drug resistance, off-target effects, and the overall difficulty of eradicating the virus, an urgent need exists to develop new drugs, especially against targets critically important for the HIV-1 life cycle. Viral entry, which involves the interaction of the surface envelope glycoprotein, gp120, with the cellular receptor, CD4, is the first step of HIV-1 infection. Gp120 has been validated as an attractive target for anti-HIV-1 drug design or novel HIV detection tools. Several small molecule gp120 antagonists are currently under investigation as potential entry inhibitors. Pyrrole, piperazine, triazole, pyrazolinone, oxalamide, and piperidine derivatives, among others, have been investigated as gp120 antagonist candidates. Herein, we discuss the current state of research with respect to the design, synthesis and biological evaluation of oxalamide derivatives and five-membered heterocycles, namely, the pyrrole-containing small molecule as inhibitors of gp120 and HIV entry.
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http://dx.doi.org/10.2174/1568026619666190717163959DOI Listing
November 2019

A simple, tandem approach to the construction of pyridine derivatives under metal-free conditions: a one-step synthesis of the monoterpene natural product, (-)-actinidine.

Chem Commun (Camb) 2019 Mar 27;55(22):3270-3273. Epub 2019 Feb 27.

Department of Pharmaceutical Sciences, College of Pharmacy, Union University, Jackson, Tennessee 38305, USA.

A simple and modular one-step synthesis of diversely substituted pyridines from readily available α,β-unsaturated carbonyl compounds and propargylic amines has been developed. The present protocol has a broad substrate scope and allows access to multi-substituted pyridines with select control of the substitution pattern under mild and metal-free conditions. The reaction involves imine formation followed by concomitant cyclization through an allenyl intermediate to afford pyridines in excellent yields, with water as the sole by-product. This mild strategy is also suitable for functionalization of natural products or other advanced intermediates having α,β-unsaturated carbonyl functionality. The utility of the present protocol was showcased with the synthesis of the monoterpene alkaloid, (-)-actinidine, an ant-associated iridoid.
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http://dx.doi.org/10.1039/c9cc01097aDOI Listing
March 2019

A Unified Strategy for the Synthesis of β-Carbolines, γ-Carbolines, and Other Fused Azaheteroaromatics under Mild, Metal-Free Conditions.

Org Lett 2018 10 1;20(20):6336-6339. Epub 2018 Oct 1.

Department of Pharmaceutical Sciences, College of Pharmacy , Union University , Jackson , Tennessee 38305 , United States.

An efficient, unified approach for the synthesis of β-carbolines, γ-carbolines, and other fused azaheteroaromatics has been realized under metal-free conditions, from propargylic amines and (hetero)aromatic aldehydes. This unified strategy provides β- and γ-carbolines as well as a range of fused azaheteroaromatics with a broad substrate scope and excellent functional group compatibility. The formal synthesis of oxopropalines D and G has been achieved on gram scale (3a), in a one-pot reaction from commercially available materials (previous shortest reported route to 3a was 5 steps). NMR studies of the conversion of imine intermediate 3aa to β-carboline 3a were conducted and revealed that the reaction proceeded through an allene intermediate.
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http://dx.doi.org/10.1021/acs.orglett.8b02441DOI Listing
October 2018

Stereocontrolled Total Synthesis of Nonenolide.

J Nat Prod 2018 06 11;81(6):1399-1404. Epub 2018 Jun 11.

Department of Chemistry , Osmania University , Hyderabad - 500007 , India.

Nonenolide (1) was first isolated from the entomopathogenic fungus Cordyceps militaries BCC2816 and exhibited good antimalarial activity against Plasmodium falciparum K1. Structurally, it features a decanolide with a trans-double bond attached to two chiral hydroxy groups, making the total synthesis of the exclusive isomer of 1 more difficult. Herein, we report the successful synthesis of 1 by employing a MacMillan α-hydroxylation to generate three chiral centers in both the key fragments, starting from 1,6-hexanediol and 1,4-butanediol, followed by Steglich esterification of compounds 2 and 3. The exclusive E-isomer was obtained via a ring-closing metathesis of the mono-PMB-protected diene 19. Deprotection provided the required natural product 1.
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http://dx.doi.org/10.1021/acs.jnatprod.8b00001DOI Listing
June 2018

A general method for the metal-free, regioselective, remote C-H halogenation of 8-substituted quinolines.

Chem Sci 2018 Feb 5;9(7):1782-1788. Epub 2018 Jan 5.

Department of Pharmaceutical Sciences , College of Pharmacy , Union University , Jackson , Tennessee , 38305 USA . Email: ; Email:

An operationally simple and metal-free protocol for geometrically inaccessible C5-H halogenation of a range of 8-substituted quinoline derivatives has been established. The reaction proceeds under air, with inexpensive and atom economical trihaloisocyanuric acid as a halogen source (only 0.36 equiv.), at room temperature. Exceptionally high generality with respect to quinoline is observed, and in most instances, the reaction proceeded with complete regioselectivity. Quinoline with a variety of substituents at the 8-position gave, exclusively, the C5-halogenated product in good to excellent yields. Phosphoramidates, tertiary amides, -alkyl/,-dialkyl, and urea derivatives of quinolin-8-amine as well as alkoxy quinolines were halogenated at the C5-position remote functionalization for the first time. This methodology provides a highly economical route to halogenated quinolines with excellent functional group tolerance, thus providing a good complement to existing remote functionalization methods of quinolin-8-amide derivatives and broadening the field of remote functionalization. The utility of the method is further showcased through the synthesis of several compounds of biological and pharmaceutical interest.
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http://dx.doi.org/10.1039/c7sc04107aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892134PMC
February 2018