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A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4- one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inhibitory activity varied widely over the series of compounds evaluated (IC50 values ranged from 0.19 to >10 muM), with excellent activity being observed for the 7,8-benzochromen-4-one and pyrimido[2,1-a] isoquinolin-4-one templates. By contrast, inhibitors based on the benzochromen-2-one (coumarin) or 2-aryl-7,8-benzochromen-4-one (flavone) scaffolds were less potent. Crucially, these studies revealed a very constrained structure-activity relationship at the 2-position of the benzopyranone and pyrimido[2,1-a]-isoquinolin-4-one pharmacophore, with only a 2-morpholino or 2-(2?-methylmorpholino) group being tolerated at this position. More detailed biological studies conducted with the most potent inhibitor NU7163 (48; IC50 = 0.19 muM) demonstrated ATP-competitive DNA-PK inhibition, with a Ki value of 24 nM, and 48 exhibited selectivity for DNA-PK compared with the related enzymes ATM, ATR, mTOR, and PI 3-K (p110alpha). Compound 48 sensitized the HeLa human tumor cell line to the cytotoxic effects of ionizing radiation in vitro, a dose modification factor of 2.3 at 10% survival being observed with an inhibitor concentration of 5 muM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.

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Pyridazine – Wikipedia,
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Extended knowledge of 35857-89-7

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A conceptually distinct strategy enabling malonylamination of alkenes with abundant amines and iodonium ylides without assistance of any transition metal was developed. Succinimide was identified as a proton shuttle that can not only largely accelerate the process of trapping highly unstable radical ion pairs with alkenes but also significantly improve the chemical yields.

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In heterogeneous catalysis, the catalyst is in a different phase from the reactants. Product Details of 89089-18-9, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 89089-18-9, name is 3-Bromo-6-chloropyridazine. In an article,Which mentioned a new discovery about 89089-18-9

Disclosed is a dehydrohalogenation method in which a halogen atom on a carbon atom in an organic compound is removed by substituting the halogen atom by a hydrogen atom. Also disclosed is a process for production of a dehalogenated compound. The dehydrohalogenation method comprises the step of treating an organic compound having a halogen atom on a carbon atom therein with a compound represented by the formula (2-1): M2BHpR1 q (2-1) or the formula (2-2): M3(BHpR1 q)2 (2-2) wherein M2 represents an alkali metal atom; M3 represents a alkali earth metal atom or a zinc atom; R1 represents a hydrogen atom, a cyano group, an acyloxy group having 2 to 13 carbon atoms or an alkoxy group having 1 to 6 carbon atoms; p represents an integer of 1 to 4; and q represents an integer of 0 to 3, provided that the sum total of p and q is 4 in a solvent in the presence of a complex of a metal belonging to Group VIII represented by the formula (1): M1XmLn (1) wherein M1 represents a metal belonging to Group VIII; X represents a halogen atom; L represents a neutral ligand; m represents an integer of 1 to 2; and n represents an integer of 2 to 3, provided that the sum total of m and n is 4.

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Pyridazine – Wikipedia,
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Reference of 35857-89-7, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.35857-89-7, Name is 6-Chloropyridazine-3-carbonitrile, molecular formula is C5H2ClN3. In a article,once mentioned of 35857-89-7

[Figure not available: see fulltext.] The morpholine (1,4-oxazinane) motif attracted significant attention due to its widespread availability in natural products and biologically relevant compounds. This review describes recent advances in the synthesis of morpholines and their carbonyl-containing analogs from 1,2-amino alcohols, aziridines, epoxides, and related compounds. Special attention is paid to the syntheses performed in a stereoselective manner and using transition metal catalysis. Selected works published since 2013 are covered.

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Reference:
Pyridazine – Wikipedia,
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Extracurricular laboratory:new discovery of 3,6-Dichloropyridazine

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Chemistry is an experimental science, and the best way to enjoy it and learn about it is performing experiments. Recommanded Product: 141-30-0. Introducing a new discovery about 141-30-0, Name is 3,6-Dichloropyridazine

Piperidinyl, pyrrolidinyl, azepinyl and piperazinyl pyridazines of formula STR1 wherein one or two carbon atoms of the STR2 moiety may be substituted with C1-4 alkyl, C1-4 alkyloxy or two carbon atoms of the CH2 groups of said moiety may be bridged with a C2-4 alkanediyl radical; X represents CH or N; R1 represents hydrogen, C1-4 alkyl, halo, hydroxy, trifluoromethyl, cyano, C1-4 alkyloxy, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkyloxycarbonyl, C1-4 alkylcarbonyl or aryl; R2 and R3 each independently represent hydrogen or C1-4 alkyl; Alk represents C1-4 alkanediyl; R4 and R5 each independently represent hydrogen, C1-4 alkyl or halo; and Het represents STR3 the addition salts and stereochemically isomeric forms thereof, said compounds having antipicornaviral activity. Pharmaceutical compositions containing these compounds as active ingredient, and a method of preparing said compounds and pharmaceutical compositions.

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Related Products of 141-30-0, A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 141-30-0, Name is 3,6-Dichloropyridazine, molecular formula is C4H2Cl2N2. In a Patent,once mentioned of 141-30-0

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

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Pyridazine – Wikipedia,
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Archives for Chemistry Experiments of 3,6-Dichloropyridazine

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In heterogeneous catalysis, the catalyst is in a different phase from the reactants. Computed Properties of C4H2Cl2N2, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 141-30-0, name is 3,6-Dichloropyridazine. In an article,Which mentioned a new discovery about 141-30-0

From an MCR fragment library, two novel chemical series have been developed as inhibitors of RET, which is a kinase involved in the pathology of medullary thyroid cancer (MTC). Structure activity relationship studies (SAR) identified two sub-micromolar tractable leads, 6g and 13g. 6g was confirmed to be a Type-II RET inhibitor. 13g and 6g inhibited RET in cells transformed by RET/C634. A RET DFG-out homology model was established and utilized to predict Type-II inhibitor binding modes.

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Pyridazine – Wikipedia,
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Brief introduction of 3-Phenyl-6-chloropyridazine

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20375-65-9, Name is 3-Phenyl-6-chloropyridazine, belongs to pyridazine compound, is a common compound. Safety of 3-Phenyl-6-chloropyridazineIn an article, once mentioned the new application about 20375-65-9.

The tetrapeptide H-Arg-Gly-Asp-Ser-OH (1) (RGDS), representing a recognition sequence of fibrinogen for its platelet receptor GP IIb-IIIa (integrin alpha(IIb)beta3), served as lead compound for the development of highly potent and selective fibrinogen receptor antagonists. Replacement of the N- terminal arginine by p-amidinophenylalanine or the Gly moiety by m- aminobenzoic acid led to compounds which are superior to the lead peptide with regard to activity and selectivity for GP IIb-IIIa vs the closely related vitronectin receptor alpha(v)beta3. By random screening [(p- amidinobenzenesulfonamido)ethyl]-p-phenoxyacetic acid derivatives have been identified as fibrinogen receptor antagonists. Further structure-activity relationship studies culminated in the preparation of N-[N-[N-(p- amidinobenzoyl)-beta-alanyl]-L-alpha-aspartyl]-3-phenyl-L-alanine (29h, Ro 43- 5054) and [[1-[N-(p-amidinobenzoyl)-L-tyrosyl]-4-piperidinyl]oxy]acetic acid (37f, Ro 44-9883), which exhibit very high activity as platelet aggregation inhibitors (IC50s 0.06 and 0.03 muM, respectively, human PRP/ADP) as well as marked selectivity for GP IIb-IIIa vs alpha(v)beta3. Since the activity of 37f in dogs declines according to a two-compartment model with an initial phase having a t( 1/2 ) of 8 min and a second phase with a t( 1/2 ) of 110 min, this compound is a suitable candidate for the development as iv platelet inhibitor.

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Pyridazine – Wikipedia,
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The Absolute Best Science Experiment for 3,6-Dichloropyridazine

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A rational design approach has been applied to synthesize a novel class of compounds with affinity for alpha1 adrenergic receptors (AR). Molecular structures are characterized by a benzimidazolylpyridazinone or an imidazolylpyridazinone moiety, an original fragment in the field of the arylpiperazine compounds with alpha1-AR blocking properties. A 1.1 nM affinity toward alpha1-AR was found for compound 3, the most active of this series.

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Pyridazine – Wikipedia,
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Electric Literature of 1121-79-5, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.1121-79-5, Name is 3-Chloro-6-methylpyridazine, molecular formula is C5H5ClN2. In a Patent,once mentioned of 1121-79-5

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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