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Optimisation of a 5-[3-phenyl-(2-cyclic-ether)-methyl-ether]-4-aminopyrrolopyrimidine series of IGF-1R inhibitors

Taking the pyrrolopyrimidine derived IGF-1R inhibitor NVP-AEW541 as the starting point, the benzyl ether back-pocket binding moiety was replaced with a series of 2-cyclic ether methyl ethers leading to the identification of novel achiral [2.2.1]-bicyclic ether methyl ether containing analogues with improved IGF-1R activities and kinase selectivities. Further exploration of the series, including a fluorine scan of the 5-phenyl substituent, and optimisation of the sugar-pocket binding moiety identified compound 33 containing (S)-2-tetrahydrofuran methyl ether 6-fluorophenyl ether back-pocket, and cis-N-Ac-Pip sugar-pocket binding groups. Compound 33 showed improved selectivity and pharmacokinetics compared to NVP-AEW541, and produced comparable in vivo efficacy to linsitinib in inhibiting the growth of an IGF-1R dependent tumour xenograft model in the mouse.

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Reference£º
Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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PIPERAZINYL PYRIMIDINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF

Provided are piperazinyl pyrimidine derivatives of formula I having CCR4 antagonism, and the preparation method, pharmaceutical composition and use thereof in the preparation of a medicament. The medicament is useful for the treatment and prevention of CCR4-related diseases.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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N-PHENYL-3-QUINAZOLIN-6-YL-BENZAMIDE DERIVATIVES AS P38 KINASE INHIBITORS

There are provided compounds of formula I, wherein R1A to R1E, R2, R3, R4A to R4C, L and X have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A

The present invention relates to novel carboxamide compounds, pharmaceutical compositions containing them, and their use in therapy. The compounds possess valuable therapeutic properties and are particularly suitable for treating or controlling medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders

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Thiomorpholine – Wikipedia,
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Aminomethyl tetrahydronaphthalene biphenyl carboxamide MCH-R1 antagonists-Increasing selectivity over hERG

Aminomethyl tetrahydronaphthalene biphenyl carboxamide MCH-R1 antagonists with greater selectivity over hERG were identified. SAR studies addressing two distinct alternatives for structural modifications leading to improve hERG selectivity are described.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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The antimalarial artemisone is an efficient heme alkylating agent

The reductive activation by iron(II)-heme of artemisone, a C-10 substituted derivative of the antimalarial artemisinin, generates covalent heme-drug adducts in high yields. This result confirms that the substitution at C-10 of artemisinin does not alter the alkylating ability of artemisin derivatives when activated by a redox-active metal center. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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OXAZOLINE DERIVATIVES FOR TREATMENT OF CNS DISORDERS

The invention relates to compounds of formula (I) wherein the definitions of X, R and R1 are provided in claim 1. It has now been found that the compounds of formula (I) have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseasessuch as Parkinson?s disease, neurodegenerative disorders such as Alzheimer?s disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadianrhythm, and cardiovascular disorders.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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MULTI-KINASE INHIBITOR COMPOUND, AND CRYSTAL FORM AND USE THEREOF

The present invention relates to a compound as represented by formula (I) or a pharmaceutically acceptable salt and stereoisomer thereof, wherein R1, R2, X, Y, P, W, and Ar are as defined in the description. The compound of formula (I) of the present invention can be used in the preparation of a drug for treating cancers mediated by abnormality of multi-kinases. Also provided is a crystal form I of a compound 4-(5-(2-chlorophenyl)-3-methyl-2,10-dihydropyrazolo[4,3-b]pyrido[4,3-e][1,4]diazepin-8-yl)morpholine, wherein in an X-ray powder diffraction pattern of crystal form I, there are characteristic peaks at 7.4¡À0.20, 17.9¡À0.2, 18.9¡À0.2, 19.4¡À0.2, 21.5¡À0.2, and 23.7¡À0.2.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Substituted piperidines as Par-1 Antagonists

The invention relates to novel substituted piperidines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular disorders and tumour disorders.

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Reference£º
Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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AMINOTRIAZOLOPYRIDINE FOR USE IN THE TREATMENT OF INFLAMMATION, AND PHARMACEUTICAL COMPOSITIONS THEREOF

The present invention relates to the novel medical use of the compound according to Formula I, in particular in the treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons. In particular, the compound inhibits JAK a family of tyrosine kinases, and more particularly JAK1. The present invention also provides pharmaceutical compositions comprising the compound, methods for the prophylaxis and/or treatment of diseases involving inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons by administering the compound.

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Reference£º
Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem