Design, synthesis, and evaluation of potential inhibitors of nitric oxide synthase

Castaño, Tania; Encinas, Arantxa; Pérez, Concepción; Castro, Ana; Campillo, Nuria E.; Gil, Carmen

doi:10.1016/j.bmc.2008.04.036

Cited by 20 publications

(14 citation statements)

References 48 publications

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“…Several substituted isothiourea derivatives were reported to possess significant cardiovascular properties as nitric oxide synthase inhibitors [1][2][3][4][5], and calcium channel blockers [6]. Isothiourea derivatives were also reported to display potent antimicrobial [7,8], anticancer [9,10], and anti-anthelmintic [11] activities.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of (Z)-3-(adamantan-1-yl)-1-(3-chlorophenyl)-S-benzylisothiourea, C₂₄H₂₇ClN₂S

El-Emam

Al-Omary

Al-Rasheed

et al. 2017

Zeitschrift Für Kristallographie - New Crystal Structures

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C 24 H 27 ClN 2 S, triclinic P1 (no. 2), a = 7.1670(3) Å, b = 12.2734(6) Å, c = 13.1560(6) Å, α = 109.605(2)°, β = 96.515(2)°, γ = 97.312(2)°, V = 1066.08(8) Å 3 , Z = 2, The asymmetric unit of the title crystal structure is shown in the figure. Tables 1 and 2 contain details on crystal structure and measurement conditions and a list of the atoms including atomic coordinates and displacement parameters. Source of materialBenzyl bromide (342 mg, 2.0 mmol) and anhydrous potassium carbonate (277 mg, 2.0 mmol) were added to a solution 1-(adamantan-1-yl)-3-(3-chlorophenyl)thiourea (642 mg, 2.0 mmol), in acetone (10 mL), and the mixture was heated under reflux for 3 h. The solvent was distilled off in vacuo, and the residue was washed with water, dried and recrystallized from ethanol to yield 625 mg (76%) of the title compound as transparent block crystals. M.P.: 367-369 K. Single crystals were obtained by slow evaporation of a EtOH/CHCl 3 (1:1) solution at room temperature.

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Section: Discussionmentioning

confidence: 99%

Crystal structure of (Z)-3-(adamantan-1-yl)-1-(3-chlorophenyl)-S-benzylisothiourea, C₂₄H₂₇ClN₂S

El-Emam

Al-Omary

Al-Rasheed

et al. 2017

Zeitschrift Für Kristallographie - New Crystal Structures

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“…In a contrast, eNOS has no known detrimental effect, but plays an important role in maintaining blood pressure and flow. Because of differing roles of these enzymes in physiology and pathology, there is an ongoing search for the respective selective inhibitors (Garvey et al, 1994;Szabo et al, 1994;Babu and Griffith, 1998;Salerno et al, 2002;Castano et al, 2008). This search included also a number of studies on isothiourea derivatives, of which two most investigated and active were, so far, ethylisothiourea and aminoethylisothiourea (Garvey et al, 1994;Southan et al, 1995;Shearer et al, 1997;Salerno et al, 2002;Xu et al, 2003;Paesano et al, 2005;Barocelli et al, 2006).…”

Section: Introductionmentioning

confidence: 96%

Synthesis and antimicrobial and nitric oxide synthase inhibitory activities of novel isothiourea derivatives

et al. 2010

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The reaction of substituted benzylhalides, or of halomethyl derivatives of thiophene or furane, with thiourea or its derivatives yielded the respective isothioureas as hydrohalide salts. The products (a total of 17, including 16 novel compounds) were tested for activity against five Gram-positive and nine Gram-negative bacterial strains, six yeast species and two protozoan species. The most active against Gram-positive bacteria were S-(2,4-dinitrobenzyl)isothiourea hydrochloride (MIC range for four out of five strains tested: 12.5-25 microg/mL) and S-(2,3,4,5,6-pentabromobenzyl)isothiourea hydrobromide (MIC range: 12.5-50 microg/mL). The lowest MICs of novel isothioureas for yeast and Gram-negative bacteria ranged between 50 and 100 microg/mL. Nine novel isothioureas showed appreciable genotoxicity in the Bacillus subtilis 'rec-assay' test, the most potent being S-2-(5-nitrofuran-2-ylmethyl)isothiourea and S-(2-nitrobenzyl) isothiourea. At 10 muM concentration, S-(3,4-dichlorobenzyl)isothiourea hydrochloride and S-(2,3,4,5,6-pentabromobenzyl)isothiourea hydrobromide inhibited Ca(2+)/calmodulin-dependent (non-inducible) nitric oxide synthase activity in normal rat brain homogenates stronger (p < 0.05) than the reference drug 7-nitroindazole (by 78, 76 and 60%, respectively); ten other new isothiourea derivatives significantly inhibited the activity to a lower extent (by 28-60%). These results extend the list of promising isothioureas with substantial activity in vitro and suggest that an in-depth study of toxicity, antimicrobial properties in vivo and nitric oxide synthase isoform selectivity of selected novel compounds is warranted.

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“…This number of numeric codes was chosen based on previous studies with ANNs. 27,35 These four variables were accomplished for each compound and stand for the chemical. The reduction dimension process is a strategy which decreases the complexity without chemical information data lost.…”

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confidence: 99%

Identification in Silico and Experimental Validation of Novel Phosphodiesterase 7 Inhibitors with Efficacy in Experimental Autoimmune Encephalomyelitis Mice

Redondo

Palomo

Brea

et al. 2012

ACS Chem. Neurosci.

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A neural network model has been developed to predict the inhibitory capacity of any chemical structure to be a phosphodiesterase 7 (PDE7) inhibitor, a new promising kind of drugs for the treatment of neurological disorders. The numerical definition of the structures was achieved using CODES program. Through the validation of this neural network model, a novel family of 5-imino-1,2,4-thiadiazoles (ITDZs) has been identified as inhibitors of PDE7.Experimental extensive biological studies have demonstrated the ability of ITDZs to inhibit PDE7 and to increase intracellular levels of cAMP. Among them, the derivative 15 showed a high in vitro potency with desirable pharmacokinetic profile (safe genotoxicity and blood brain barrier penetration). Administration of ITDZ 15 in an experimental autoimmune encephalomyelitis (EAE) mouse model results in a significant attenuation of clinical symptoms, showing the potential of ITDZs, especially compound 15, for the effective treatment of multiple sclerosis.

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Design, synthesis, and evaluation of potential inhibitors of nitric oxide synthase

Cited by 20 publications

References 48 publications

Crystal structure of (Z)-3-(adamantan-1-yl)-1-(3-chlorophenyl)-S-benzylisothiourea, C₂₄H₂₇ClN₂S

Crystal structure of (Z)-3-(adamantan-1-yl)-1-(3-chlorophenyl)-S-benzylisothiourea, C₂₄H₂₇ClN₂S

Synthesis and antimicrobial and nitric oxide synthase inhibitory activities of novel isothiourea derivatives

Identification in Silico and Experimental Validation of Novel Phosphodiesterase 7 Inhibitors with Efficacy in Experimental Autoimmune Encephalomyelitis Mice

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Design, synthesis, and evaluation of potential inhibitors of nitric oxide synthase

Cited by 20 publications

References 48 publications

Crystal structure of (Z)-3-(adamantan-1-yl)-1-(3-chlorophenyl)-S-benzylisothiourea, C24H27ClN2S

Crystal structure of (Z)-3-(adamantan-1-yl)-1-(3-chlorophenyl)-S-benzylisothiourea, C24H27ClN2S

Synthesis and antimicrobial and nitric oxide synthase inhibitory activities of novel isothiourea derivatives

Identification in Silico and Experimental Validation of Novel Phosphodiesterase 7 Inhibitors with Efficacy in Experimental Autoimmune Encephalomyelitis Mice

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Product

Resources

About

Crystal structure of (Z)-3-(adamantan-1-yl)-1-(3-chlorophenyl)-S-benzylisothiourea, C₂₄H₂₇ClN₂S

Crystal structure of (Z)-3-(adamantan-1-yl)-1-(3-chlorophenyl)-S-benzylisothiourea, C₂₄H₂₇ClN₂S