Advances in the synthesis and recent therapeutic applications of 1,2,4-thiadiazole heterocycles

Castro, Ana; Castaño, Tania; Encinas, Arantxa; Porcal, Williams; Gil, Carmen

doi:10.1016/j.bmc.2005.10.012

Cited by 142 publications

(54 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For instance, thiadiazoles are considered bioisosteres of oxadiazole, oxazole, pyrimidine, and so forth. 43 Substitution of a thiadiazole with its bioisostere can lead to different compounds with a prospect of improving biological activities, such as better liposolubility. 44 1,3,4-Thiadiazoles are also mesoionic with dense, highly polarizable character that promotes stronger interaction with the amino-acid residues forming the receptor binding site.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Mechanism and Site of Inhibition of AMPA Receptors: Pairing a Thiadiazole with a 2,3-Benzodiazepine Scaffold

Wang

Yao

et al. 2013

ACS Chem. Neurosci.

View full text Add to dashboard Cite

2,3-Benzodiazepine compounds are synthesized as drug candidates for treatment of various neurological disorders involving excessive activity of AMPA receptors. Here we report that pairing a thiadiazole moiety with a 2,3-benzodiazepine scaffold via the N-3 position yields an inhibitor type with >28-fold better potency and selectivity on AMPA receptors than the 2,3-benzodiazepine scaffold alone. Using wholecell recording, we characterized two thiadiazolyl compounds, that is, one contains a 1,3,4-thiadiazole moiety and the other contains a 1,2,4-thiadiazole-3-one moiety. These compounds exhibit potent, equal inhibition of both the closed-channel and the open-channel conformations of all four homomeric AMPA receptor channels and two GluA2R-containing complex AMPA receptor channels. Furthermore, these compounds bind to the same receptor site as GYKI 52466 does, a site we previously termed as the "M" site. A thiadiazole moiety is thought to occupy more fully the side pocket of the receptor site or the "M" site, thereby generating a stronger, multivalent interaction between the inhibitor and the receptor binding site. We suggest that, as a heterocycle, a thiadiazole can be further modified chemically to produce a new class of even more potent, noncompetitive inhibitors of AMPA receptors.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Mechanism and Site of Inhibition of AMPA Receptors: Pairing a Thiadiazole with a 2,3-Benzodiazepine Scaffold

Wang

Yao

et al. 2013

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Thus, the reaction of 290 with aliphatic or aromatic isocyanates gives the sparingly soluble 3-oxothiadiazolium salts 291, which, in the presence of moist air, hydrolyzes to 1,2,4-thiadiazolidine-3,5-diones 292 with evolution of hydrogen chloride (Scheme 14.69) [169,170].…”

Section: 24-thiadiazolidinesmentioning

confidence: 99%

Thiadiazoles

Chiacchio

Romeo

2011

Modern Heterocyclic Chemistry

View full text Add to dashboard Cite

“…[46] Другие же аналоги 2-имино-4-тиобиурета применяются в качестве актопротек-торов -синтетических препаратов, препятствующих развитию утомления и повышающих работоспособ-ность. [47,48] Diaminothiadiazoles…”

Section: 5-диамино-124-тиадиазолunclassified