Heterocyclic Building Blocks-Thiomorpholine

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Clogging the ubiquitin-proteasome machinery with marine natural products: Last decade update

The ubiquitin-proteasome pathway (UPP) is the central protein degradation system in eukaryotic cells, playing a key role in homeostasis maintenance, through proteolysis of regulatory andmisfolded (potentially harmful) proteins. As cancer cells produce proteins inducing cell proliferation and inhibiting cell death pathways, UPP inhibition has been exploited as an anticancer strategy to shift the balance between protein synthesis and degradation towards cell death. Over the last few years, marine invertebrates and microorganisms have shown to be an unexhaustive factory of secondary metabolites targeting the UPP. These chemically intriguing compounds can inspire clinical development of novel antitumor drugs to cope with the incessant outbreak of side effects and resistance mechanisms induced by currently approved proteasome inhibitors (e.g., bortezomib). In this review, we report about (a) the role of the UPP in anticancer therapy, (b) chemical and biological properties of UPP inhibitors from marine sources discovered in the last decade, (c) high-throughput screening techniques for mining natural UPP inhibitors in organic extracts. Moreover, we will tell about the fascinating story of salinosporamide A, the first marine natural product to access clinical trials as a proteasome inhibitor for cancer treatment.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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[1, 2, 4] Triazolo [1, 5 – a] pyridine compound and its preparation method and medical use (by machine translation)

The present invention relates to [1, 2, 4] triazolo [1, 5 – a] pyridine compound and its preparation method and medical use. In particular, the invention relates to compounds of the general formula I shown, its preparation method and containing pharmaceutical compositions of the compounds, and their use as JAK kinase inhibitors, the compound and its containing pharmaceutical compositions of the compounds can be used for treating diseases associated with JAK kinase activity, such as inflammation, autoimmune disorders, such as cancer. Wherein the general formula I in the definition of each substituent as defined in the specification. (by machine translation)

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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5-amido-indole-2-carboxamide derivatives

The present invention relates to compounds of formula I [image] wherein G and R1 to R5 and R12 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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TETRAZOLE COMPOUNDS AS CALCIUM CHANNEL BLOCKERS

The present invention relates to novel tetrazole compounds; to processes for their preparation; to pharmaceutical compositions containing the compounds; and to the use of the compounds in therapy to treat diseases for which blocking the Cav2.2 calcium channels is beneficial. Formula (I) wherein A is: (II) or (III)

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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PYRIDINE DERIVATIVE AND MEDICINE

The main purpose of the invention is to provide a novel pyridine derivative or a pharmaceutically acceptable salt thereof. Examples of the invention include a pyridine derivative represented by general formula [1], and a pharmaceutically acceptable salt thereof. This compound or a pharmaceutically acceptable salt thereof exhibits mGluR5 inhibitory activity, and can therefore be used as an agent for the prevention or treatment of, e.g., pain (for example, acute pain, chronic pain, inflammatory pain, neuropathic pain, hyperalgesia, thermal hyperalgesia, allodynia, pain due to noxious thermal stimulation, pain due to noxious mechanical stimulation, pain in the lower urinary tract or reproductive organs, or migraine), pruritus, lower urinary tract symptoms or lower urinary tract dysfunctions, gastroesophageal reflux disease (GERD), gastroesophageal reflux associated with transient lower esophageal sphincter relaxation (TLESR), and diseases of the central nervous system.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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INHIBITORS OF JANUS KINASES

The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2). The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 and TYK2 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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4- (4-(HETEROCYCLYLALKOXY}PHENYL)-1-(HETEROCYCLYL-CARBONYL)PIPERIDINE DERIVATIVES AND RELATED COMPOUNDS AS HISTAMINE H3 ANTAGONISTS FOR THE TREATMENT OF NEUROLOGICAL DISEASES SUCH AS ALZHEIMER’S

The present invention provides, in a first aspect, a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein: R1 represents-C1-6 alkyl-O-C1-6 alkyl,-C3-8 cycloalkyl, aryl, heterocyclyl, heteroaryl and other groups; X represents a bond, O, CO, OCH2, CH2 O or SO2; Z represents CO, CONR10 or SO2; R10 represents hydrogen, C1-6 alkyl,-C3-8 cycloalkyl, aryl, heterocyclyl, heteroaryl; A represents a single or a double bond; m and n independently represent 0, 1 or 2; R2 represents hydrogen, C1-6 alkyl or C1-6 alkoxy; R3 represents halogen, C1-6 alkyl, hydroxy, C1-6 alkoxy, cyano, amino,-COC1-6 alkyl,-SO2C1-6 alkyl or trifluoromethyl; R4 represents-(CH2)q-NR11R12 or a group of formula (i) wherein all the other substituents are as defined in claim 1. Compounds of formula (I) and their pharmaceutically acceptable salts have affinity for and are antagonists and/or inverse agonists of the histamine H3 receptor and are believed to be of potential use in the treatment of neurological diseases including Alzheimer’s disease.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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SUBSTITUTED BENZOTHIOPHENYL DERIVATIVES AS GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (I) wherein R1, R2, R3, R5, R6, W, and A are defined herein.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

Electric Literature of 39093-93-1, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, and a compound is mentioned, 39093-93-1, Thiomorpholine 1,1-dioxide, introducing its new discovery.

The discovery and optimization of a novel class of potent, selective, and orally bioavailable anaplastic lymphoma kinase (ALK) inhibitors with potential utility for the treatment of cancer

A class of 2-acyliminobenzimidazoles has been developed as potent and selective inhibitors of anaplastic lymphoma kinase (ALK). Structure based design facilitated the rapid development of structure-activity relationships (SAR) and the optimization of kinase selectivity. Introduction of an optimally placed polar substituent was key to solving issues of metabolic stability and led to the development of potent, selective, orally bioavailable ALK inhibitors. Compound 49 achieved substantial tumor regression in an NPM-ALK driven murine tumor xenograft model when dosed qd. Compounds 36 and 49 show favorable potency and PK characteristics in preclinical species indicative of suitability for further development.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Discovery of aryl-substituted indole and indoline derivatives as RORgammat agonists

A series of aryl-substituted indole and indoline derivatives were discovered as novel RORgammat agonists by a scaffold-based hybridization of the reported RORgammat agonists 1 and 2. SAR studies on the core structures, the RHS hydrophilic side chains and the LHS hydrophobic aryl groups of a hybrid compound 3 led to the identification of potent RORgammat agonists with improved drug-like properties. Compound 14 represented a high potency lead with an EC50 of 20.8 ¡À 1.5 nM, the (S)-enantiomer (EC50 = 16.1 ¡À 4.5 nM) of which was 17 times more potent than the (R) counterpart (EC50 = 286 ¡À 30.4 nM) in RORgamma dual FRET assay. The cell-based GAL4 reporter gene assay also suggested 14 as the most active compound which exhibited an EC50 of 247 ¡À 33.1 nM and a maximum activation percentage of 133%. Moreover, 14 showed high metabolic stability (t1/2 = 113 min) in mouse liver microsome and had improved aqueous solubility at pH 7.4 compared to the parent compounds. Furthermore, 14 was found to be orally bioavailable and demonstrated excellent in vivo pharmacokinetics in mice. Present studies indicate that 14 deserves further investigation in tumor animal models as a potential candidate of RORgammat agonist for cancer immunotherapy.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem