40106-16-9

Usage

InChI:InChI=1/C13H19NO2S/c1-2-16-13(15)11-9-7-5-3-4-6-8-10(9)17-12(11)14/h2-8,14H2,1H3

Upstream product

• 502-49-8 cycloactanone 
• 105-56-6 ethyl 2-cyanoacetate 
• 33018-58-5 ethyl 2-cyano-2-cyclooctanylideneacetate 

Downstream Products

• 1314118-57-4 2-amino-N-(3-chlorobenzyl)-4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide 
• 1314118-56-3 2-amino-N'-phenyl-4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carbohydrazide 
• 588692-42-6 2-amino-N-benzyl-4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide 
• 1416053-11-6 ethyl-2-(2-iodobenzamido)-4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxylate 

Relevant academic research and scientific papers

Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor

We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs that retain robust negative cooperativity, such as 3. Herein, we report the synthesis and functional profiling of analogues of 3, placing specific emphasis on examining secondary and tertiary amino substituents at the 4-position, combined with a range of substituents at the 5/6-positions (e.g. aromatic/aliphatic carbocycles). We identify analogues with diverse pharmacology at the D2R including NAMs with sub-μM affinity (9h) and, surprisingly, low efficacy partial agonists (9d and 9i).

One-Pot Synthesis of Thieno[3,2- e]pyrrolo[1,2- a]pyrimidine Derivative Scaffold: A Valuable Source of PARP-1 Inhibitors

A new, efficient, and versatile one-pot cascade reaction of diverse Gewald's aminothiophenes, 2-hydroxy-4-oxobut-2-enoic acid, and derivatives of cyanoacetic acid catalyzed by Et3N is presented. It enables direct synthesis of diverse 1-(2-oxoethylidene)-2-oxothieno[3,2-e]pyrrolo[1,2-a]pyrimidine in good to excellent yields. The reaction exhibits a broad substrate scope and also presents an opportunity for further modification of the structure. The method offers a convenient practical alternative to the known procedures. The synthesized thieno[3,2-e]pyrrolo[1,2-a]pyrimidine scaffold is an important structural motif of new poly(ADP-ribose) polymerase (PARP) inhibitors, playing a useful role in multiple pharmacological applications.

Exploitation of Conformational Dynamics in Imparting Selective Inhibition for Related Matrix Metalloproteinases

Matrix metalloproteinases (MMPs) have numerous physiological functions and share a highly similar catalytic domain. Differential dynamical information on the closely related human MMP-8, -13, and -14 was integrated onto the benzoxazinone molecular template. An in silico library of 28,099 benzoxazinones was generated and evaluated in the context of the molecular-dynamics information. This led to experimental evaluation of 19 synthesized compounds and identification of selective inhibitors, which have potential utility in delineating the physiological functions of MMPs. Moreover, the approach serves as an example of how dynamics of closely related active sites may be exploited to achieve selective inhibition by small molecules and should find applications in other enzyme families with similar active sites.

A Thieno[2,3- d]pyrimidine Scaffold Is a Novel Negative Allosteric Modulator of the Dopamine D2 Receptor

Recently, a novel negative allosteric modulator (NAM) of the D2-like dopamine receptors 1 was identified through virtual ligand screening. This ligand comprises a thieno[2,3-d]pyrimidine scaffold that does not feature in known dopaminergic ligands. Herein, we provide pharmacological validation of an allosteric mode of action for 1, revealing that it is a NAM of dopamine efficacy and identify the structural determinants of this allostery. We find that key structural moieties are important for functional affinity and negative cooperativity, while functionalization of the thienopyrimidine at the 5- and 6-positions results in analogues with divergent cooperativity profiles. Successive compound iterations have yielded analogues exhibiting a 10-fold improvement in functional affinity, as well as enhanced negative cooperativity with dopamine affinity and efficacy. Furthermore, our study reveals a fragment-like core that maintains low μM affinity and robust negative cooperativity with markedly improved ligand efficiency.

Facile assembly of two 6-membered fused N-heterocyclic rings: A rapid access to novel small molecules via Cu-mediated reaction

A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for facile assembly of two six membered fused N-heterocyclic rings leading to novel small molecules as potential inhibitors of PDE4. The Royal Society of Chemistry.

The synthesis and biological evaluation of 2-amino-4,5,6,7,8,9- hexahydrocycloocta[b]thiophenes as allosteric modulators of the A1 adenosine receptor

A series of 2-amino-4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes were prepared and evaluated as potential allosteric modulators of the A1 adenosine receptor (AR). The structure-activity relationships of the 3-position were explored along with va

NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS

The present application relates to cannabinoid receptor ligands containing compounds of formula (I) wherein A, R1, R2, and R3 are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

Microwave accelerated Gewald reaction: synthesis of 2-aminothiophenes

Microwave-promoted synthesis of 2-aminothiophenes by multicomponent reactions of a ketone with an active nitrile and elemental sulfur under KF-alumina catalysis is described.

A new class of small molecule RNA polymerase inhibitors with activity against Rifampicin-resistant Staphylococcus aureus1

The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase.