Terminal Phenyl Ring Research Articles

Synthesis, Docking Study and Biological Evaluation of Amide-Based Soluble Epoxide Hydrolase Inhibitors with Novel Secondary Pharmacophore of Pyrimidin-2-ol.

Soluble epoxide hydrolase enzyme (sEH) is one of the most promising and emerging targets to develop drugs for multiple disease indications, including hypertension, diabetes, stroke, dyslipidemia, pain, etc. Most inhibitor scaffolds have a urea or amide moiety to mimic the active-site transition state. In this regard, we developed a series of amide sEH inhibitors with a pyrimidin-2-ol ring as a new secondary pharmacophore, which was subjected to in vitro evaluation. Compound 4w (4-chloro-N-{4-[6-(4-chlorophenyl)-2-hydroxypyrimidin-4-yl]phenyl}benzamide), which contains 4-chloro substituent in both terminal phenyl rings, exhibited the most inhibitory activity against sEH with an IC50 value of 1.2 nM. Molecular docking analysis of the synthesized compounds revealed that the greater number of hydrogen bonding interactions of the amide group as the primary pharmacophore with Asp-353, Tyr-383, and Tyr-466 as the key catalytic residue triad of the enzyme played a critical role and led to a more favorable binding affinity. Pharmacokinetic properties of the synthesized compounds were calculated in silico, and all ADMET indices fell within acceptable ranges. Altogether, the results of this work could provide useful information on 4,6-diphenylpyrimidin-2-olas sEH inhibitors which can be utilized in further development in this area.

Leveraging structural and 2D-QSAR to investigate the role of functional group substitutions, conserved surface residues and desolvation in triggering the small molecule-induced dimerization of hPD-L1

Small molecules are rising as a new generation of immune checkpoints’ inhibitors, with compounds targeting the human Programmed death-ligand 1 (hPD-L1) protein are pioneering this area of research. Promising examples include the recently disclosed compounds from Bristol-Myers-Squibb (BMS). These molecules bind specifically to hPD-L1 through a unique mode of action. They induce dimerization between two hPD-L1 monomers through the hPD-1 binding interface in each monomer, thereby inhibiting the PD-1/PD-L1 axis. While the recently reported crystal structures of such small molecules bound to hPD-L1 reveal valuable insights regarding their molecular interactions, there is still limited information about the dynamics driving this unusual complex formation. The current study provides an in-depth computational structural analysis to study the interactions of five small molecule compounds in complex with hPD-L1. By employing a combination of molecular dynamic simulations, binding energy calculations and computational solvent mapping techniques, our analyses quantified the dynamic roles of different hydrophilic and lipophilic residues at the surface of hPD-L1 in mediating these interactions. Furthermore, ligand-based analyses, including Free-Wilson 2D-QSAR was conducted to quantify the impact of R-group substitutions at different sites of the phenoxy-methyl biphenyl core. Our results emphasize the importance of a terminal phenyl ring that must be present in any hPD-L1 small molecule inhibitor. This phenyl moiety overlaps with a very unfavorable hydration site, which can explain the ability of such small molecules to trigger hPD-L1 dimerization.

Induction of the smectic A phase in liquid crystalline mixtures formulated using non-chiral compounds with positive and negative dielectric anisotropy

ABSTRACT The induction of the SmA phase in mixtures of non-chiral nematic compounds with the positive and the negative dielectric anisotropy is presented which is obtained by different substitutions of fluorine atoms. One component is a three-ring tolane with polar group – OCF3 in position 4 and two fluorine atoms in positions 3 and 5 in the terminal phenyl ring. The other component is two ring tolane with two or four fluorine atoms in the lateral position. Based on phase diagrams, the influence of the alkyl chain length of both types of compounds on the induction phenomenon is shown. Results of the X-ray measurements confirm that the induced phase is a monolayer SmA phase. The increase of the alkyl chain length causes the increase in the strength of the induction in mixtures, i.e. the induced SmA phase is observed for a wider range of the temperature and concentration of mixture components.

Synthesis and hemagglutination inhibitory properties of mannose-tipped ligands: The effect of terminal phenyl groups and the linker between the mannose residue and the triazole moiety

Two families (A, B) of triazole conjugates derived from d-mannose possessing reversed linkage functionality were easily assembled by Cu(I) catalyzed azide-alkyne cycloaddition reaction (CuAAC). The mannose precursors were built with either 3-azidopropyl or propargyl aglycones whereas the phenyl moieties were built with terminal azide or propargyl groups, respectively. In a hemagglutination inhibition (HAI) assay, family A (7a-11a), where the linker between the mannose residue and the triazole ring is three carbons displayed a 3–5 fold enhancement in activity compared to family B (13a-17a) having methyl-triazolyl moiety. The representative ligand 7a, where the terminal phenyl ring is substituted with an ester group and Cl atom exhibited the highest inhibitory activity with an HAI titer of 8 μM. This compound could be a good candidate for the further design of potent mannosyl ligands targeting FimH fimbrial lectin.

4-Chloro-5-(di-methyl-amino)-2-[(5-phenyl-1,3,4-oxa-diazol-2-yl)meth-yl]pyridazin-3(2H)-one.

In the structure of the title compound, C15H14ClN5O2, the terminal phenyl ring and the adjacent furan ring subtend a dihedral angle of 6.77 (17)°. The 4-chloro-5-(di-methyl-amino)-pyridazin-3(2H)-one group is linked to the oxa-diazole ring by a methyl-ene bridge, and the dihedral angle between the pyridazine and oxa-diazole rings is 88.66 (14)°. In the crystal, C-H⋯O and C-H⋯N hydrogen bonds extend the structure into a three-dimensional network.

13C NMR investigations and order parameters of rod-like molecules with terminal phenyl and thiophene rings in mesogenic core✰

Rod-like mesogens with the rigid core constituted by a combination of phenyl and thiophene moieties reveal interesting orientational ordering behavior. In this article, four rod-like mesogens constructed with a terminal alkoxy chain on only one side of the mesogenic core with the other end terminated with either a phenyl or thiophene ring have been investigated using 13C NMR spectroscopy. The mesogen with the terphenyl moiety in the core exhibited polymesomorphism with nematic, smectic C, and smectic I mesophases with very high clearing temperatures. The replacement of terphenyl with terthiophene moiety resulted in suppression of polymesomorphism, with only nematic mesophase being observed. Mesogens with single terminal thiophene connected to two phenyl rings in the core also showed only the nematic mesophase for both the possibilities of linking the core to the thiophene ring at the 2- and 3- positions. One- and two- dimensional 13C NMR spectra have been obtained in the mesophases from which the alignment induced chemical shifts of the ring carbons and 13C-1H dipolar couplings, as well as the local order parameters, have been obtained. The considerable difference in 13C chemical shifts and the 13C-1H dipolar couplings of thiophene ring with change in position of the linking unit is attributed to the difference in the order parameters of the thiophene moiety between the two cases. The data obtained on the ordering of phenyl and thiophene rings in the core units offered information into the effect of replacing the phenyl ring with the thiophene ring. So also, the change of position of the link to the thiophene moiety provided important insights into the orientational behavior in the liquid crystalline phase and on the molecular structure.

Novel 4-phenoxypyridine derivatives bearing imidazole-4-carboxamide and 1,2,4-triazole-3-carboxamide moieties: Design, synthesis and biological evaluation as potent antitumor agents

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against MKN-45, A549 and H460 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activities. The most promising compound T14 (with c-Met IC50 value of 0.012 μM) showed remarkable antiproliferative activities against MKN-45, A549 and H460 cell lines with IC50 values of 0.64 μM, 1.92 μM and 2.68 μM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that imidazole-4-carboxamide was more preferred as linker part, and electron-withdrawing groups (especially halogen groups) on the terminal phenyl rings were beneficial for improving the antitumor activities.

Synthesis and crystal structure of racemic (R*,R*)-2,2'-(1,4-phenyl-ene)bis-(3-phenyl-2,3,5,6-tetra-hydro-4H-1,3-thia-zin-4-one).

In the racemic title compound, C26H24N2O2S2, one of the thia-zine rings shows a twisted boat conformation (Q = 0.743 Å, θ = 92.1°) and the other a half-chair puckering (Q = 0.669 Å, θ = 54.3°). The terminal phenyl rings are almost parallel to each other [dihedral angle 21.71 (10)°]. Both of these rings are orthogonal to the central phenyl ring, subtending a dihedral angle of about 78° in each case. The extended structure is consolidated by C-H⋯O and C-H⋯S hydrogen bonds as well as aromatic ring inter-actions of parallel-displaced and T-type. The mol-ecule has approximate C2 local symmetry but this is not carried over to its three-dimensional structure or the inter-molecular inter-actions.

Structure-Activity Relationship Studies on Novel Antiviral Agents for Norovirus Infections.

Human norovirus is the leading cause of acute gastroenteritis worldwide, affecting every year 685 million people. Norovirus outbreaks are associated with very significant economic losses, with an estimated societal cost of 60 billion USD per year. Despite this, no therapeutic options or vaccines are currently available to treat or prevent this infection. An antiviral therapy that can be used as treatment and as a prophylactic measure in the case of outbreaks is urgently needed. We previously described the computer-aided design and synthesis of novel small-molecule agents able to inhibit the replication of human norovirus in cell-based systems. These compounds are non-nucleoside inhibitors of the viral polymerase and are characterized by a terminal para-substituted phenyl group connected to a central phenyl ring by an amide-thioamide linker, and a terminal thiophene ring. Here we describe new modifications of these scaffolds focused on exploring the role of the substituent at the para position of the terminal phenyl ring and on removing the thioamide portion of the amide-thioamide linker, to further explore structure-activity relationships (SARs) and improve antiviral properties. According to three to four-step synthetic routes, we prepared thirty novel compounds, which were then evaluated against the replication of both murine (MNV) and human (HuNoV) norovirus in cells. Derivatives in which the terminal phenyl group has been replaced by an unsubstituted benzoxazole or indole, and the thioamide component of the amide-thioamide linker has been removed, showed promising results in inhibiting HuNoV replication at low micromolar concentrations. Particularly, compound 28 was found to have an EC50 against HuNoV of 0.9 µM. Although the most active novel derivatives were also associated with an increased cytotoxicity in the human cell line, these compounds represent a very promising starting point for the development of new analogues with reduced cytotoxicity and improved selectivity indexes. In addition, the experimental biological data have been used to create an initial 3D quantitative structure-activity relationship model, which could be used to guide the future design of novel potential anti-norovirus agents.

Cytotoxic 1,2,3-Triazoles as Potential Leads Targeting the S100A2-p53 Complex: Synthesis and Cytotoxicity.

In silico screening predicted 1 (N-(4-((4-(3-(4-(3-methoxyphenyl)-1H-1,2,3-triazol-1-yl)propyl)piperazin-1-yl) sulfonyl)-phenyl)acetamide) as an inhibitor of the S100A2-p53 protein-protein interaction. S100A2 is a validated pancreatic cancer drug target. In the MiaPaCa-2 pancreatic cell line, 1 was a ∼50 μM growth inhibitor. Synthesis of five focused compound libraries and cytotoxicity screening revealed increased activity from the presence of electron withdrawing moieties on the sulfonamide aromatic ring, with the 3,5-bis-CF3 Library 3 analogues the most active, with GI50 values of 0.91 (3-ClPh; 13 i; BxPC-3, Pancreas) to 9.0 μM (4-CH3 ; 13 d; PANC-1, Pancreas). Activity was retained against an expanded pancreatic cancer cell line panel (MiaPaCa-2, BxPC-3, AsPC-1, Capan-2, PANC-1 and HPAC) and the normal cell line MCF10A (breast). Bulky 4-disposed substituents on the terminal phenyl ring enhanced broad spectrum activity with growth inhibition values spanning 1.1 to 3.1 μM (4-C(CH3 )3 ; 13 e; BxPC-3 and AsPC-1 (pancreas), respectively). Central alkyl spacer contraction from propyl to ethyl proved detrimental to activity with Library 4 and 5.5- to 10-fold less cytotoxic than the propyl linked Library 2 and Library 3. The data herein was consistent with the predicted binding poses of the compounds evaluated. The highest levels of cytotoxicity were observed with those analogues best capable of adopting a near identical pose to the p53-peptide in the S100A2-p53 binding groove.

Low cytotoxic quinoline-4-carboxylic acids derived from vanillin precursors as potential human dihydroorotate dehydrogenase inhibitors

Twenty novel 2-substituted quinoline-4-carboxylic acids bearing amide moiety were designed and synthesized by Doebner reaction. Human dihydroorotate dehydrogenase (hDHODH) was recognized as a biological target and all compounds were screened as potential hDHODH inhibitors in an enzyme inhibition assay. The prepared heterocycles were also evaluated for their cytotoxic effects on the healthy HaCaT cell line while lipophilic properties were considered on the basis of experimentally determined logD values at physiological pH. The most promising compound 5j, with chlorine at para-position of terminal phenyl ring, showed good hDHODH inhibitory activity, low cytotoxicity, and optimal lipophilicity. The bioactive conformation of 5j on the hDHODH, determined by means of molecular docking, revealed the compound’s pharmacology and provide guidelines for further lead optimization.

Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidine derivatives containing 1,8-naphthyridine-4-one fragment.

In this study, a series of pyrrolo [2,3-d]pyrimidine derivatives containing 1,8-naphthyridine-4-one fragment were synthesized and their biological activity were tested. Most of the target compounds displayed moderate to excellent activity against one or more cancer cell lines and low activity against human normal cell LO2 invitro. The most promising compound 51, of which the IC50 values were 0.66μM, 0.38μM and 0.44μM against cell lines A549, Hela and MCF-7, shown more remarkable activity and better apoptosis effect than the positive control Cabozantinib. The structure-activity relationships (SARs) indicated that double-EWGs (such as R3=2-Cl-4-CF3) on the terminal phenyl rings was a key factor in improving the biological activity. In addition, the further research on compound 51 mainly included c-Met kinase activity and selectivity, concentration dependence, and molecular docking.

Effect of replacing the terminal phenyl ring with 3-pyridyl and inversion of imine linkage on the mesophase behaviour of four-ring azo/ester/Schiff base compounds

ABSTRACT In the present work two homologue series of four-ring azo/ester/imine compounds; namely, 4-(4′–alkoxy–phenylazo) phenyl–4′′–(benzylidene–amino) benzoate, I n, and 4–(4′–alkoxy–phenylazo) phenyl–4′′–[(pyridin-3–ylmethylene)–amino] benzoate, II n, were prepared and investigated for their mesophase behaviour. In these two types of homologue series, the length of the terminal alkoxy group (n) varies between 6 and 16 carbons. Compounds prepared in both series were structurally characterised via thermogravimetric and elemental analyses, FTIR, 1H-NMR, and mass spectroscopy. Their mesophase transition temperatures were determined by differential scanning calorimetry (DSC), whereas, the type of the mesophase was identified by polarised light microscopy (PLM). The molecular structure–property relationship was conducted aiming to investigate the effect of replacing the terminal phenyl group in I n with a pyridyl one in II n, in addition to the effect of variation of the alkoxy chain length. Aiming to investigate the effect of inversion of the methineazo group on the mesophase behaviour of the compounds, a comparison was made between the prepared series of compounds (I n) with previously prepared four rings 4-(4′-alkoxyphenylazo)–phenyl 4′′–phenyliminomethyl–benzoate phenyl-4ʹ-(4′′-alkoxyphenylazo) benzoate, III n. Finally, the mesophases of series II n were compared with their corresponding three-ring analogues, 4-(4′-alkoxy phenyl −4′′-[(pyridin-4-ylmethylene)–amino] benzoate analogues (IV n).

Efficient Synthesis of π-Conjugated Organic Molecules Utilizing Cross-Coupling Reactions and Application to Electronic Devices

The development of efficient synthetic methods of π-conjugated compounds by means of cross-coupling reactions are reported. Tetraarylethenes with four different substituents are synthetic targets. The Pt-catalyzed addition of diboron to alkynylsilanes to yield 1-aryl-1-silyl-2,2-diborylethenes with perfect stereoselectivity. Step by step chemoselective Suzuki-Miyaura couplings with aryl halides were performed to give a triarylsilylethene with perfect chemoselectivity. The silyl group was transformed to the aryl group with desilybromination, followed by Suzuki-Miyaura coupling, leading to the successful synthesis of the desired tetraarylated olefin. On the other hand, novel and versatile methods for the synthesis of various phenacene and thienophenacene derivatives by cross-coupling reactions were elucidated for application to organic field-effect transistors (OFETs) and organic photovoltaics (OPVs). As one of representative phenacenes, picene is a polycyclic aromatic hydrocarbon consisting of five fused benzene rings with a W-shape structure, which exhibits high hole mobility. We successfully found the synthetic route of various substituted picenes. In addition, the synthesis of phenanthro [1,2-b : 8,7-b’] dithiophene (PDT) was achieved by replacing two terminal phenyl rings in picene with thiophene rings. The fabricated OFET devices based on C12-PDT-2 displayed a quite high mobility of up to 5.6 cm2 V−1 s−1. In regard to OPV devices, PDT-fluorinated benzothiadiazole (BT) polymers possessing alkyl side chains showed the highest power conversion efficiencies (PCE) of 9.0%.

Modification of imidazothiazole derivatives gives promising activity in B-Raf kinase enzyme inhibition; synthesis, in vitro studies and molecular docking

B-Raf mutation was identified as a key target in cancer treatment. Based on structural features of dabrafenib (potent FDA approved B-Raf inhibitor), the design of new NH2-based imidazothiazole derivatives was carried out affording new highly potent derivatives of imidazothiazole-based scaffold with amino substitution on the terminal phenyl ring as well as side chain with sulfonamide group and terminal substituted phenyl ring. In vitro enzyme assay was investigated against V600E B-Raf kinase. Compounds 10l, 10n and 10o showed higher inhibitory activities (IC50 = 1.20, 4.31 and 6.21 nM, respectively). In vitro cytotoxicity evaluation was assessed against NCI-60 cell lines. Most of tested derivatives showed cytotoxic activities against melanoma cell line. Compound 10k exhibited most potent activity (IC50 = 2.68 µM). Molecular docking study revealed that the new designed derivatives preserved the same binding mode of dabrafenib with V600E B-Raf active site. It was investigated that the new modification in the synthesized derivatives (substituted with NH2) had a significant inhibitory activity towards V600E B-Raf. This core scaffold is considered a key compound for further structural and molecular optimization.

Mol-ecular and crystal structure, optical properties and DFT studies of 1,4-dimeth-oxy-2,5-bis-[2-(4-nitro-phen-yl)ethen-yl]benzene.

The title compound DBNB, C24H20N2O6, has been crystallized and studied by X-ray diffraction, spectroscopic and computational methods. In the title mol-ecule, which is based on a 1,4-distyryl-2,5-di-meth-oxy-benzene core with p-nitro-substituted terminal benzene rings, the dihedral angle between mean planes of the central fragment and the terminal phenyl ring is 16.46 (6)°. The crystal packing is stabilized by π-π inter-actions. DFT calculations at the B3LYP/6-311 G(d,p) level of theory were used to compare the optimized structures with the experimental data. Energy parameters, including HOMO and LUMO energies, their difference, and vertical excitation and emission energies were obtained.

Design, Synthesis and Biological Evaluation of Novel 4-phenoxypyridine Derivatives Containing Semicarbazones Moiety as Potential c-Met Kinase Inhibitors.

The Hepatocyte Growth Factor Receptor (HGFR) c-Met is over-expressed and/or mutated in various human tumor types. Dysregulation of c-Met/HGF signaling pathway affects cell proliferation, survival and motility, leading to tumor growth, angiogenesis, and metastasis. Therefore, c-Met has become an attractive target for cancer therapy. This study is aimed to evaluate a new series of 4-phenoxypyridine derivatives containing semicarbazones moiety for its cytotoxicity. A series of novel 4-phenoxypyridines containing semicarbazone moieties were synthesized and evaluated for their in vitro cytotoxic activities against MKN45 and A549 cancer cell lines and some selected compounds were further examined for their inhibitory activity against c-Met kinase. In order to evaluate the mechanism of cytotoxic activity of compound 24, cell cycle analysis, Annexin V/PI staining assay, AO/EB assay, wound-healing assay and docking analysis with c-Met were performed. The results indicated that most of the compounds showed moderate to good antitumor activity. The compound 28 showed well cytotoxic activity against MKN45 and A549 cell lines with IC50 values of 0.25μM and 0.67μM, respectively. Compound 24 showed good activity on c-Met and its IC50 value was 0.093μM. Their preliminary Structure-Activity Relationships (SARs) studies indicated that electronwithdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity. Treatments of MKN45 cells with compound 24 resulted in cell cycle arrest in G2/M phase and induced apoptosis in a dose-dependent manner. In addition, AO/EB assays indicated 24 induced dose-dependent apoptosis of A549 and MKN45 cells. Wound-healing assay results indicated that compound 24 strongly inhibited A549 cell motility.

Computational Investigations on the Binding Mode of Ligands for the Cannabinoid-Activated G Protein-Coupled Receptor GPR18.

GPR18 is an orphan G protein-coupled receptor (GPCR) expressed in cells of the immune system. It is activated by the cannabinoid receptor (CB) agonist ∆9-tetrahydrocannabinol (THC). Several further lipids have been proposed to act as GPR18 agonists, but these results still require unambiguous confirmation. In the present study, we constructed a homology model of the human GPR18 based on an ensemble of three GPCR crystal structures to investigate the binding modes of the agonist THC and the recently reported antagonists which feature an imidazothiazinone core to which a (substituted) phenyl ring is connected via a lipophilic linker. Docking and molecular dynamics simulation studies were performed. As a result, a hydrophobic binding pocket is predicted to accommodate the imidazothiazinone core, while the terminal phenyl ring projects towards an aromatic pocket. Hydrophobic interaction of Cys251 with substituents on the phenyl ring could explain the high potency of the most potent derivatives. Molecular dynamics simulation studies suggest that the binding of imidazothiazinone antagonists stabilizes transmembrane regions TM1, TM6 and TM7 of the receptor through a salt bridge between Asp118 and Lys133. The agonist THC is presumed to bind differently to GPR18 than to the distantly related CB receptors. This study provides insights into the binding mode of GPR18 agonists and antagonists which will facilitate future drug design for this promising potential drug target.

Design, synthesis and biological evaluation of novel N-[4-(2-fluorophenoxy)pyridin-2-yl]cyclopropanecarboxamide derivatives as potential c-Met kinase inhibitors

Three series of novel 4-phenoxypyridine derivatives containing 4-methyl-6-oxo-1,6-dihydropyridazine- 3-carboxamide, 5-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide and 4-methyl-3,5-dioxo-2,3,4,5- tetrahydro-1,2,4-triazine-6-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activitives against c-Met kinase and cytotoxic activitives against A549, H460, HT-29 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activitives. The most promising compound 26a (with c-Met IC50 value of 0.016 μM) showed remarkable cytotoxicity against A549, H460, and HT-29 cell lines with IC50 values of 1.59 μM, 0.72 μM and 0.56 μM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that 4-methyl-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxamide was more preferred as linker part, and electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activitives. Furthermore, the colony formation, acridine orange/ethidium bromide (AO/EB) staining, apoptosis, and wound-healing assay of 26a were performed on HT-29 and/or A549 cell lines.

Effective tuning of optical storage devices using photosensitive bent-core liquid crystals

Abstract We discuss three series of substituted resorcinol based bent-core liquid crystals with azobenzene wings, substituents consisting of methyl (-CH3) and halogens ( F, Cl, Br) on the resorcinol core connected to azobenzene wings with variable alkoxy chains. The effect of electron-donating (-CH3) and electron-withdrawing (halogens) group on the photoisomerization and thermal back relaxation studied using UV–Vis spectroscopy. 4-methyl resorcinol bent-core (BC) exhibits the longest thermal back relaxation of about 16.33 h; whereas, the fluoro substituted BCs show the shortest relaxation time of 4.0 h. In the case of fluoro/bromo lateral substituted BCs at terminal azobenzene phenyl ring in 4-methyl resorcinol exhibits longer thermal back relaxation time of ~16.16 h, which is noteworthy. These results envisage the effect of substituents on the central unit as well as the lateral and/or terminal position of azobenzene wings on the photoisomerization. The reversible trans (E) - cis (Z) isomerization occurs in 60 s and 4–16 h, respectively. The prolonged thermal back relaxation attributed to the diazo linkage and the polar substituents. A prototype of optical storage device tested under crossed polarisers at λ = 365 nm, the change from order to disorder state upon illumination with the bright and dark regions was visible and represents ideal candidates for optical storage devices. Compiled results show powerful tuning of structure-property effects using light as external stimuli.