Inspiration for revival of old drug: Improving solubility and avoiding hygroscopicity of pipemidic acid by forming two pharmaceutical salts based on charge-assisted hydrogen bond recognitions

2021 ◽  
Author(s):  
Yunan Zhang ◽  
Yu Duan ◽  
Jin Su ◽  
Lixin Liu ◽  
Yanru Feng ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Aqueous Solubility ◽  
Pipemidic Acid ◽  
Pharmaceutical Salts

In order to improve the solubility of pipemidic acid (PPA) which belongs to quinolones and becomes an "old drug" due to it possesses low aqueous solubility which restricting its application,...

scholarly journals Defining desirable natural product derived anticancer drug space: optimization of molecular physicochemical properties and ADMET attributes

ADMET & DMPK ◽  
2016 ◽  
Vol 4 (2) ◽  
pp. 98 ◽  
Author(s):  
Deepika Singh
Keyword(s):  
Hydrogen Bond ◽  
Natural Products ◽  
Physicochemical Properties ◽  
Natural Product ◽  
Aqueous Solubility ◽  
Cancer Drug ◽  
Log P ◽  
Drug Candidates ◽  
Anti Cancer ◽  
Property Space

<p class="ADMETabstracttext">As part of our endeavor to enhance survival of natural product derived drug candidates and to guide the medicinal chemist to design higher probability space for success in the anti cancer drug development area, we embarked on a detailed study of the property space for a collection of natural product derived anti cancer molecules. We carried out a comprehensive analysis of properties for 24 natural products derived anti cancer drugs including clinical development candidates and a set of 27 natural products derived anti cancer lead compounds. In particular, we focused on understanding the interplay among eight physicochemical properties including like partition coefficient (log P), distribution coefficient at pH=7.4 (log D), topological polar surface area (TPSA), molecular weight (MW), aqueous solubility (log S), number of hydrogen bond acceptors (HBA), number of hydrogen bond donors (HBD) and number of rotatable bonds (n<sub>Rot</sub>) crucial for drug design and  relationships between physicochemical properties, ADME (absorption, distribution, metabolism, and elimination) attributes, and in silico toxicity profile for these two sets of compounds. This analysis provides guidance for the chemist to modify the existing natural product scaffold or designing of new anti cancer molecules in a property space with increased probability of success and may lead to the identification of druglike candidates with favorable safety profiles that can successfully test hypotheses in the clinic.</p>

Tetrahydroberberine pharmaceutical salts/cocrystals with dicarboxylic acids: Charge-assisted hydrogen bond recognitions and solubility regulation

2019 ◽  
Vol 1197 ◽  
pp. 377-385 ◽  
Author(s):  
Yu-nan Zhang ◽  
Ying-li Liu ◽  
Li-xin Liu ◽  
Yan-ru Feng ◽  
Da-jun Zhang ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Dicarboxylic Acids ◽  
Pharmaceutical Salts

Optimisation of aqueous solubility in a series of G protein coupled receptor 119 (GPR119) agonists

MedChemComm ◽  
2013 ◽  
Vol 4 (1) ◽  
pp. 95-100 ◽  
Author(s):  
James S. Scott ◽  
Alan M. Birch ◽  
Katy J. Brocklehurst ◽  
Hayley S. Brown ◽  
Kristin Goldberg ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
G Protein ◽  
Aqueous Solubility ◽  
G Protein Coupled Receptor ◽  
Hydrogen Bond Acceptor ◽  
G Protein Coupled

Solubility improvements in a series of GPR119 agonists are achieved through reduction of lipophilicity together with hydrogen bond acceptor modulation.

scholarly journals A new amino acid for improving permeability and solubility in macrocyclic peptides through side chain-to-backbone hydrogen bonding.

2022 ◽  
Author(s):  
Jaru Taechalertpaisarn ◽  
Satoshi Ono ◽  
Okimasa Okada ◽  
Timothy C. Johnstone ◽  
R. Scott Lokey
Keyword(s):  
Hydrogen Bond ◽  
Membrane Permeability ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Aqueous Solubility ◽  
Side Chain ◽  
Dependent Manner ◽  
Peptide Backbone ◽  
Cyclic Hexapeptide ◽  
Intramolecular Hydrogen

Despite the notoriously poor membrane permeability of peptides in general, many cyclic peptide natural products show high passive membrane permeability and potently inhibit a variety of “undruggable” intracellular targets. A major impediment to designing cyclic peptides with good permeability is the high desolvation energy associated with the peptide backbone amide NH groups. Strategies for mitigating the deleterious effect of the backbone NH group on permeability include N-methylation, steric occlusion, and the formation of intramolecular hydrogen bonds with backbone carbonyl oxygens, while there have been relatively few studies on the use of polar side chains to sequester backbone NH groups. We investigated the ability of N,N-pyrrolidinyl glutamine (Pye), whose side chain contains a powerful hydrogen bond accepting C=O amide group but no hydrogen bond donors, to sequester exposed backbone NH groups in a series of cyclic hexapeptide diastereomers. Analyses of partition coefficients, lipophilic permeability efficiencies (LPE), artificial and cell-based permeability assays revealed that specific Leu-to-Pye substitutions conferred dramatic improvements in aqueous solubility and permeability in a scaffold- and position-dependent manner. Introduction of the Pye residue thus offers a complementary tool, alongside traditional approaches, for improving membrane permeability and solubility in cyclic peptides.

Solubility Enhancement of Poorly Soluble Drug Simvastatin by Solid Dispersion Technique

2016 ◽  
Vol 2 (2) ◽  
pp. 91-95
Author(s):  
Neelima Rani T ◽  
Pavani A ◽  
Sobhita Rani P ◽  
Srilakshmi N
Keyword(s):  
Dissolution Rate ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Onset Of Action ◽  
Kneading Method ◽  
Wetting Property ◽  
Poorly Soluble ◽  
Dispersion Technique ◽  
Low Solubility

This study aims to formulate solid dispersions (SDs) of Simvastatin (SIM) to improve the aqueous solubility, dissolution rate and to facilitate faster onset of action. Simvastatin is a BCS class II drug having low solubility & therefore low oral bioavailability. In the present study, SDs of simvastatin different drug-carrier ratios were prepared by kneading method. The results showed that simvastatin solubility & dissolution rate enhanced with polymer SSG in the ratio 1:7 due to increase in wetting property or possibly may be due to change in crystallinity of the drug.

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