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FLUORINE-SUBSTITUTED INDAZOLE COMPOUNDS AND USES THEREOF

Fluorine-substituted indazole compounds, pharmaceutical compositions containing these compounds and uses thereof. The compounds and pharmaceutical compositions can be used as soluble guanylate cyclase simulators.

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Thiomorpholine | C4H9NS – PubChem

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1,1-DIOXO-THIOMORPHOLINYL INDOLYL METHANONE DERIVATIVES

The present invention relates to compounds of formula I wherein R1, R2 and G 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,
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PYRIDO[4,3-B]PYRAZINE-2-CARBOXAMIDES AS NEUROGENIC AGENTS FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS

The present invention relates to compounds of general formula (I), wherein R1 is hydrogen; R2 is hydrogen, lower alkyl, benzyl, lower alkyl substituted by hydroxy or is cycloalkyl optionally substituted by cyano; or R1 and R2 form together with the N-atom to which they are attached a heterocycloalkyl group, optionally containing an additional N, O or S ring atom, and which is optionally substituted by hydroxy; R3 is halogen, phenyl optionally substituted by one or more halogen, cyano, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or by lower alkyl substituted by hydroxy, or is heteroaryl, optionally substituted by lower alkyl or halogen, or is 3,6-dihydro-pyran-4-yl, or is piperidin-1-yl optionally substituted by one or more halogen; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to it corresponding enantiomer and/or optical isomer thereof. The compounds of formula I may be used in the treatment of schizophrenia, obsessive-compulsive personality disorder, depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson’s disease, dementia, Alzheimer’s disease, cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington’s disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, selected from alcohol, opiates, methamphetamine, phencyclidine and cocaine.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Synthesis & Biological Activity of Some New Carboxamides, Carbohydrazides & Carbamates Derived from 2,3-Dihydro-5(H)-oxothiazolo<3,2-a>pyrimidine-6-carboxylic Acid

Some new carboxamides (Va-j), carbohydrazides (Vk-p) and carbamates (VIIIa-d) derived from 2,3-dihydro-5(H)-oxothiazolo<3,2-a>pyrimidine-6-carboxylic acid (III) have been synthesised and evaluated for their antiinflammatory, antibacterial, antifungal and anthelmintic activities.The carboxamides (Ve,i,j) and carbohydrazides (Vk,n,o) possess promising antiinflammatory activity against carrageenin-induced paw oedema in rats, compound Ve being the most active member of the series showing 50.8 percent inhibition at 200 mg/kg (p.o.) dose.Ve, however, is found to be inactive at lower doses.None of the compounds shows any noteworthy antibacterial, antifungal or anthelmintic activities except Vk which displays promising antitubercular activity in vitro (MIC=5 mcg/ml) against Mycobacterium tuberculosis H37Rv.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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3-ARYL AND HETEROARYL SUBSTITUTED 5-TRIFLUOROMETHYL OXADIAZOLES AS HISTONE DEACETYLASE 6 (HDAC6) INHIBITORS

The present invention is directed to substituted 5-trifluoromethyl oxadiazole compounds of generic formula (I) or a pharmaceutically acceptable salt thereof. In particular, the invention is directed to a class of aryl and heteroaryl substituted 5-trifluoromethyl oxadiazole compounds of formula I which may be useful as HDAC6 inhibitors for treating cellular proliferative diseases, including cancer, neurodegenerative diseases, such as schizophrenia and stroke, as well as other diseases.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF INFLAMMATORY DISORDERS

The present invention discloses pharmaceutical compositions comprising: a compound according to Formula I: useful in the prophylaxis and/or treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving degradation and/or disruption of cartilage homeostasis, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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ANTIBACTERIAL QUINOLINE DERIVATIVES

The present invention relates to novel substituted quinoline derivatives according to the general Formula (Ia) or Formula (Ib): including any stereochemically isomeric form thereof, a pharmaceutically acceptable salt thereof, a N-oxide form thereof or a solvate thereof. The claimed compounds are useful for the treatment of a bacterial infection. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the claimed compounds, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of a bacterial infection and a process for preparing the claimed compounds.

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FUSED TRICYCLIC COMPOUNDS AS NOVEL mTOR INHIBITORS

The present invention provides Fused Tricyclic Compounds of the Formula (1) wherein Q, R1, R2, R3, and R4 are as defined herein, and pharmaceutically acceptable salts of such Fused Tricyclic Compounds. The Fused Tricyclic Compounds are useful in the treatment of cancer and other proliferative disorders

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Piperidine and piperazine inhibitors of fatty acid amide hydrolase targeting excitotoxic pathology

FAAH inhibitors offer safety advantages by augmenting the anandamide levels ?on demand? to promote neuroprotective mechanisms without the adverse psychotropic effects usually seen with direct and chronic activation of the CB1 receptor. FAAH is an enzyme implicated in the hydrolysis of the endocannabinoid N-arachidonoylethanolamine (AEA), which is a partial agonist of the CB1 receptor. Herein, we report the discovery of a new series of highly potent and selective carbamate FAAH inhibitors and their evaluation for neuroprotection. The new inhibitors showed potent nanomolar inhibitory activity against human recombinant and purified rat FAAH, were selective (>1000-fold) against serine hydrolases MGL and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Evaluation of FAAH inhibitors 9 and 31 using the in vitro competitive activity-based protein profiling (ABPP) assay confirmed that both inhibitors were highly selective for FAAH in the brain, since none of the other FP-reactive serine hydrolases in this tissue were inhibited by these agents. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on known FAAH cocrystal structures. To rationally design new molecules that are irreversibly bound to FAAH, we have constructed ?precovalent? FAAH-ligand complexes to identify good binding geometries of the ligands within the binding pocket of FAAH and then calculated covalent docking poses to select compounds for synthesis. FAAH inhibitors 9 and 31 were evaluated for neuroprotection in rat hippocampal slice cultures. In the brain tissue, both inhibitors displayed protection against synaptic deterioration produced by kainic acid-induced excitotoxicity. Thus, the resultant compounds produced through rational design are providing early leads for developing therapeutics against seizure-related damage associated with a variety of disorders.

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Compounds, compositions, and methods for stimulating neuronal growth and elongation

The present invention concerns methods, pharmaceutical compounds, and compositions for stimulating neuroite outgrowth in nerve cells leading to nerve regeneration. These methods, compounds and compositions inhibit rotamase enzyme activity associated with binding proteins.

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