Heterocyclic Building Blocks-Thiomorpholine

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Targeting of Fumarate Hydratase from Mycobacterium tuberculosis Using Allosteric Inhibitors with a Dimeric-Binding Mode

With the growing worldwide prevalence of antibiotic-resistant strains of tuberculosis (TB), new targets are urgently required for the development of treatments with novel modes of action. Fumarate hydratase (fumarase), a vulnerable component of the citric acid cycle in Mycobacterium tuberculosis (Mtb), is a metabolic target that could satisfy this unmet demand. A key challenge in the targeting of Mtb fumarase is its similarity to the human homolog, which shares an identical active site. A potential solution to this selectivity problem was previously found in a high-throughput screening hit that binds in a nonconserved allosteric site. In this work, a structure-activity relationship study was carried out with the determination of further structural biology on the lead series, affording derivatives with sub-micromolar inhibition. Further, the screening of this series against Mtb in vitro identified compounds with potent minimum inhibitory concentrations.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Trisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials

In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound (13) showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED90 of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead molecule with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

Chemistry is traditionally divided into organic and inorganic chemistry. Safety of Thiomorpholine 1,1-dioxide, The former is the study of compounds containing at least one carbon-hydrogen bonds.In a patent£¬Which mentioned a new discovery about 39093-93-1

PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA

Provided are compounds of formula (I) or a pharmaceutically acceptable salts or stereoisomer thereof, which are PI3K-delta inhibitors, and are useful for the treatment of PI3K-delts-mediated diseases such as inflammation, asthma, COPD and cancer.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Triazolo[1,5-c]pyrimidines and bronchodilation use thereof

1,2,4-Triazolo[1,5-c]pyrimidines substituted at the 7 position through a nitrogen atom which is part of a 1-oxo- or 1,1-dioxothiomorpholine ring have been found to have potent bronchodilator activity. Pharmacological methods of using these compounds and pharmaceutical compositions containing these compounds are also disclosed.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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PROCESS FOR PREPARATION OF PYRIDINE DERIVATIVES

The present invention relates to a process for the manufacture of compounds of formula wherein the substituents are as described herein which comprises the steps of a) reacting a compound of formula with a compound of formula to form a compound of formula b) converting the OH/=O function of compounds of formula XIV/XIVa into a leaving group P with a reagent containing a leaving group, selected from POCl3, PBr3, MeI and (F 3CSO2)2O to form a compound of formula wherein P is halogen or trifluoromethanesulfonate; c) substituting R2 for the leaving group P by reacting compound XV with HR2 to form a compound of formula and d) hydrolyzing the nitrile function in an acidic medium selected from H2SO4, HCl and acetic acid, to form a compound of formula I The compounds of formula I are valuable intermediates for the manufacture of therapeutically active compounds which have NK-1 antagonist activity.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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IMIDAZOPYRIDINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY

A series of imidazo[l,2-a]pyridine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4)

Inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. Herein we described our lead optimization studies including the synthesis, molecular docking studies and structure-activity relationship (SAR) studies of a series of novel heteroaryldihydropyrimidine (HAP) inhibitors of HBV capsid assembly inhibitors, and the discovery of a potent inhibitor of HBV capsid assembly of GLS4 (ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-methyl]-2-[2-thiazolyl]-1,4-dihydro-pyrimidine-5-carboxylate) which is now in clinical phase 2. GLS4 demonstrated potent inhibitory activities in HBV HepG2.2.15 cell assay with an EC50value of 1 nM, and it also exhibited high potency against various drug-resistant HBV viral strains with EC50values in the range of 10?20 nM, more potent than the typical HBV polymerase inhibitors such as lamivudine, telbivudine, and entecavir. Pharmacokinetic profiles of GLS4 were favorable and safety evaluation including acute toxicity and repeated toxicity study indicated that GLS4 was safe enough to support clinical experiments in human.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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PROCESS FOR THE PREPARATION OF ISOXAZOLYL-METHOXY-NICOTINIC ACIDS

The present invention relates to a process for the preparation of a compound of formula (I) which is useful as an intermediate in the preparation of active pharmaceutical compounds from a compound of formula (IV) wherein R1 and R2 are as defined herein,.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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SUBSTITUTED PIPERIDINYLTETRAHYDROQUINOLINES

The present application relates to novel substituted piperidinyltetrahydroquinolines, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of diabetic microangiopathies, diabetic ulcers on the extremities, in particular for promoting wound healing of diabetic foot ulcers, diabetic heart failure, diabetic coronary microvascular heart disorders, peripheral and cardial vascular disorders, thromboembolic disorders and ischaemias, peripheral circulatory disturbances, Raynaud’s phenomenon, CREST syndrome, microcirculatory disturbances, intermittent claudication, and peripheral and autonomous neuropathies.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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ALKYNYL PHOSPHINE GOLD COMPLEXES FOR TREATING BACTERIAL INFECTIONS

A compound of formula (I) for use in the prevention or treatment of a bacterial infection.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem