Diastereomeric complex of (R/S)-piperidine-3-carboxylic acid with (2R,3R)-tartaric acid: Structural, spectroscopic and computational studies

Abstract This study addressed the possibility of forming of co-amorphous systems between clozapine (CZ) and various carboxylic acid plasticizers (CAPs). The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation methodology at drug/plasticizer stoichiometric ratios of 1:1, 1:1.5 and 1:2. Solid state characterization was performed using differential scanning calorimetry, X-ray diffraction and infra red spectroscopy. Highly soluble homogeneous co-amorphous dispersions were formed between clozapine and CAPs via hydrogen bonding. The co-amorphous dispersions formed with tartaric acid (1:2) showed the highest dissolution percentage (> 95 % in 20 minutes) compared to pure crystalline CZ (56 %). Highly stable solutions were obtained from co-amorphous CZ-citric and CZ-tartaric acid at 1:1.5 molar ratio. The prepared dispersions suggest the possibility of peroral or sublingual administration of highly soluble clozapine at a reduced dose with the great chance to bypass the first pass metabolism.

Download Full-text

Synthesis of chromium(III) complex with 1-hydroxy-2-pyridinone-6-carboxylic acid as insulin-mimetic agent and its spectroscopic and computational studies

Journal of Molecular Structure ◽

10.1016/j.molstruc.2012.07.041 ◽

2013 ◽

Vol 1031 ◽

pp. 144-151 ◽

Cited By ~ 9

Author(s):

Nuttawisit Yasarawan ◽

Khajadpai Thipyapong ◽

Somsak Sirichai ◽

Vithaya Ruangpornvisuti

Keyword(s):

Carboxylic Acid ◽

Computational Studies ◽

Insulin Mimetic

Download Full-text

Synthesis and Reactivity of Bicycles Derived from Tartaric Acid and α-Amino Acids: A Novel Class of Conformationally Constrained Dipeptide Isosteres Based upon Enantiopure 3-Aza-6,8-dioxabicyclo[3.2.1]octane-7-carboxylic Acid

The Journal of Organic Chemistry ◽

10.1021/jo9904967 ◽

1999 ◽

Vol 64 (20) ◽

pp. 7347-7364 ◽

Cited By ~ 34

Author(s):

Antonio Guarna ◽

Antonio Guidi ◽

Fabrizio Machetti ◽

Gloria Menchi ◽

Ernesto G. Occhiato ◽

...

Keyword(s):

Amino Acids ◽

Carboxylic Acid ◽

Tartaric Acid ◽

Conformationally Constrained

Download Full-text

1,2-Difunctionalized bicyclo[1.1.1]pentanes: Long–sought-after mimetics for ortho/meta-substituted arenes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2108881118 ◽

2021 ◽

Vol 118 (28) ◽

pp. e2108881118

Author(s):

Jin-Xin Zhao ◽

Yu-Xuan Chang ◽

Chi He ◽

Benjamin J. Burke ◽

Michael R. Collins ◽

...

Keyword(s):

Carboxylic Acid ◽

Building Blocks ◽

Matched Pairs ◽

Computational Studies

The development of a versatile platform for the synthesis of 1,2-difunctionalized bicyclo[1.1.1]pentanes to potentially mimic ortho/meta-substituted arenes is described. The syntheses of useful building blocks bearing alcohol, amine, and carboxylic acid functional handles have been achieved from a simple common intermediate. Several ortho- and meta-substituted benzene analogs, as well as simple molecular matched pairs, have also been prepared using this platform. The results of in-depth ADME (absorption, distribution, metabolism, and excretion) investigations of these systems are presented, as well as computational studies which validate the ortho- or meta-character of these bioisosteres.

Download Full-text