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Myma bioactivated thioalkylbenzoxazole prodrug family active against mycobacterium tuberculosis

Screening of a GSK-proprietary library against intracellular Mycobacterium tuberculosis identified 1, a thioalkylbenzoxazole hit. Biological profiling and mutant analysis revealed that this compound is a prodrug that is bioactivated by the mycobacterial enzyme MymA. A hit-expansion program including design, synthesis, and profiling of a defined set of analogues with optimized drug-like properties led to the identification of an emerging lead compound, displaying potency against intracellular bacteria in the low micromolar range, high in vitro solubility and permeability, and excellent microsomal stability.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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TRIOXACARCIN-ANTIBODY CONJUGATES AND USES THEREOF

Provided herein are trioxacarcin-antibody drug conjugates of Formula (I): and pharmaceutically acceptable salts thereof, wherein R7 is -L-B, wherein L is a linking group, and B is an antibody or antibody fragment. Also provided are methods of preparing the antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the trioxacarcin- antibody drug conjugates (e.g., compounds of Formula (II), novel trioxacarcins without an antibody conjugated thereto), pharmaceutical compositions thereof, and methods of their use and treatment.

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1,3,4-OXADIAZOLE SULFAMIDE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel compounds. The novel compounds, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present invention have histone deacetylase (HDAC) inhibitory activity and are effective for the prevention or treatment of HDAC6-mediated diseases, including infectious diseases; neoplasms; endocrine, nutritional and metabolic diseases; mental and behavioral disorders; neurological diseases; diseases of the eye and adnexa; cardiovascular diseases; respiratory diseases; digestive diseases; diseases of the skin and subcutaneous tissue; diseases of the musculoskeletal system and connective tissue; or congenital malformations, deformations and chromosomal abnormalities.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures

Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development. We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t1/2 > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 A resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-Aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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HEXAHYDROPYRROLO[3,4-C]PYRROLE DERIVATIVES USEFUL AS LOX INHIBITORS

The disclosure relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein X1 and X5 is each selected from CR1 or N; X2, X3 and X4 is each selected from CR1, CR2 or N, provided at least one of X2, X3 and X4 is CR2 and provided only one of X1, X2, X3, X4 and X5 can be N. R1, R2, R3, R4, R5, L1, L2 and L3 are as defined herein. Compounds according to Formula (I) are pharmacologically effective as lysyl oxidase (LOX) inhibitors and are believed to be useful in the treatment of, for instance, cancer.

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Thiomorpholine – Wikipedia,
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NOVEL GAMMA AMINOBUTYRIC ACID TYPE A RECEPTOR MODULATORS FOR MOOD DISORDERS

The present invention relates to novel alpha5 subunit-selective negative allosteric modulators of GABAA receptors that have been deuterated to improve their medicinal properties by prolonging their half-lives, rendering them useful as fast-acting pharmaceutical treatments for depression related disorders.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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An Overview of Recent Advances in the Applications of Click Chemistry in the Synthesis of Bioconjugates with Anticancer Activities

The click chemistry is one of the most powerful C?N bond forming-reactions towards five-membered heterocycles. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) has widely used in the discovery of anti-cancer drugs and many articles have been published in this field. This review article aims to review general mechanism aspects and the recent advances (2016?2019) of click chemistry for cancer therapy.

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Synthetic method JAKAK1 inhibitor Filgogogotinib (by machine translation)

The invention provides Filgogogotinib, which comprises the following steps: (1) reacting 2 – amino -6 -bromopyridine with p-methylbenzene derivatives, and preparing compound 1; (2) reacting compound 1 with hydroxylamine hydrochloride, N, N – diisopropylethylamine to obtain compound 2; (3) reacting compound 2 with thiomorpholine 3, 4 dioxides, thereby obtaining Filgogogotinib.) . compound (3) and compound (4) are reacted, yielding compound 5, compound [4], and azodiisobutyronitrile to react, and the compound 5; (6 1 -) 5 is reacted with the azodiisobutyronitrile -1. The route of synthesizing Filgogogou is firstly coupled and then closed loop, the raw material is cheap, the reaction operation is simple, the product is easy to purify, the yield is high, and the method is suitable for commercial scale production. (by machine translation)

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Thiomorpholine – Wikipedia,
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COMPOUNDS AND COMPOSITIONS AS SYK KINASE INHIBITORS

Provided here in area novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated Syk kinase activity

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Thiomorpholine – Wikipedia,
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CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USES RELATED THERETO

The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. The receptor modulators can be formulated to form pharmaceutical compositions comprising the disclosed compounds or pharmaceutically acceptable salts or prodrugs thereof. The compositions may be used for managing CXCR4 related conditions, typically prevention or treatment of viral infections abnormal cellular proliferation, retinal degeneration, inflammatory diseases, or as an immunostimulant or immunosuppressant or for managing cancer and may be administered with another active ingredient such as an antiviral agent or chemotherapeutic agent.

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Thiomorpholine – Wikipedia,
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