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The present invention relates to compounds of formula I. The compounds are inhibitors of the Src Homolgy-2 phosphatase (SHP2) and thus useful in the treatment of Noonan Syndrome, Leopard Syndrome and cancer.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1801N – PubChem

 

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486-73-7, Name is Isoquinoline-1-carboxylic acid, belongs to isoquinoline compound, is a common compound. Recommanded Product: Isoquinoline-1-carboxylic acidIn an article, once mentioned the new application about 486-73-7.

A new catalytic system for enantioselective [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one with thioacetylene derivatives is described. The use of a catalytic amount (20-30 mol%) of copper(II) salt with chiral bis-pyridine ligand was found to be effective in promoting the [2+2]-cycloaddition reaction, furnishing the corresponding bicyclic compound in good yield and good enantioselectivity.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1959N – PubChem

 

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The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1beta converting enzyme (“ICE”) inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1-(“IL-1”), apoptosis-, interferon-gamma inducing factor-(IGIF), or interferon-gamma-(“IFN-gamma”) mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting caspase activity and decreasing IGIF production and IFN-gamma production and methods for treating interleukin-1, apoptosis-, and interferon-gamma-mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention. ”

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1819N – PubChem

 

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Rational Drug Design of Topically Administered Caspase 1 Inhibitors for the Treatment of Inflammatory Acne

The use of an interleukin beta antibody is currently being investigated in the clinic for the treatment of acne, a dermatological disorder affecting 650M persons globally. Inhibiting the protease responsible for the cleavage of inactive pro-IL1beta into active IL-1beta, caspase-1, could be an alternative small molecule approach. This report describes the discovery of uracil 20, a potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment of inflammatory acne. The uracil series was designed according to a published caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent reversible inhibition and an aryl moiety in P4 for selectivity against the apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or by using different substrate concentrations. In addition to classical structure-activity-relationship exploration, topical administration challenges such as phototoxicity, organic and aqueous solubility, chemical stability in solution, and skin metabolic stability are discussed and successfully resolved.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Application of 486-73-7, 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. 486-73-7, Name is Isoquinoline-1-carboxylic acid, molecular formula is C10H7NO2. In a Patent,once mentioned of 486-73-7

METABOTROPIC GLUTAMATE RECEPTOR ANTAGONISTS AND THEIR USE FOR TREATING CENTRAL NERVOUS SYSTEM DISEASES

The present invention provides compounds, and pharmaceutical compositions containing those compounds, that are active at metabotropic glutamate receptors. The compounds are useful for treating neurological diseases and disorders. Methods of preparing the compounds also are disclosed.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1794N – PubChem

 

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Application of 486-73-7, 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.486-73-7, Name is Isoquinoline-1-carboxylic acid, molecular formula is C10H7NO2. In a article,once mentioned of 486-73-7

Pd-catalyzed decarboxylative cross-coupling of 2-carboxyazine N-oxides with various (hetero)aryl halides

Decarboxylative cross-coupling reactions of substituted 2-carboxyazine N-oxides, with a variety of (hetero)aryl halides, by bimetallic Pd 0/CuI and Pd0/AgI catalysis are reported. Two possible pathways, a conventional bimetallic-catalyzed decarboxylative arylation, as well as a protodecarboxylative/direct C-H arylation sequence have been considered. These methods provide the first general decarboxylative arylation methodology for the 2-carboxyazine series. Choose your pathway: Decarboxylative cross-coupling reactions of substituted 2-carboxyazine N-oxides, with a variety of (hetero)aryl halides, by bimetallic Pd0/CuI and Pd0/AgI catalysis are reported (see figure). These methods provide the first general decarboxylative arylation methodology in the 2-carboxyazine series.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1938N – PubChem

 

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Development of potent serotonin-3 (5-HT3) receptor antagonists. II. Structure-activity relationships of N-(1-benzyl-4-methylhexahydro-1H-1,4- diazepin-6-yl)carboxamides

Our studies on 4-amino-5-chloro-2-ethoxybenzamides led to the discovery that the N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl)benzamide 9 and the 1- benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 10 are potent serotonin-3 (5-HT3) receptor antagonists. Structure-activity relationship (SAR) studies on the influence of the aromatic nucleus of 9 and 10 upon inhibition of the von Bezold-Jarisch reflex in rats are described. Heteroaromatic rings such as pyrrole, thiophene, furan, pyridine, pyridaziae, 1,2-benzisoxazole, indole, quinoline, and isoquinoline rings showed weak 5-HT3 receptor antagonistic activity. Within this series, use of the 1H-indazole ring as an aromatic moiety led to a substantial increase of the activity; the 1H- indazolylcarboxamides 54, 57, 97, and 102 showed potent 5-HT3 receptor antagonistic activity. The optimal compound identified via extensive SAR studies was N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-1H-indazole- 3-carboxamide (54), whose effect was superior to that of the corresponding benzamide 10 and essentially equipotent to those of ondansetron (1) and granisetron (4).

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1873N – PubChem

 

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AMIDE SUBSTITUTED IMIDAZOQUINOLINES

Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain amide functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Synthesis, and evaluation of in vitro and in vivo anticancer activity of 14-substituted oridonin analogs: A novel and potent cell cycle arrest and apoptosis inducer through the p53-MDM2 pathway

A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Among them, compound C7 (IC50 = 0.16 muM) exhibited the most potent anti-proliferative activity against HCT116 cells; it was about 43- and 155-fold more efficacious than that of oridonin (IC50 = 6.84 muM) and 5-Fu (IC50 = 24.80 muM) in HCT116 cancer cells. Interestingly, the IC50 value of compound C7 in L02 normal cells was 23.6-fold higher than that in HCT116 cells; it exhibited better selective anti-proliferative activity and specificity than oridonin and 5-Fu. Furthermore, compound C7 possibly induced cell cycle arrest and apoptosis by regulating the p53-MDM2 signalling pathway. Notably, C7 displayed more significant suppression of tumour growth than oridonin in colon tumour xenograft models where the tumour growth inhibition rate was 85.82%. Therefore, compound C7 could be a potential lead compound for the development of a novel antitumour agent.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Cobalt(II) and nickel(II) complexes of isoquinoline-1-carboxylate

Trans-Diaquabis(isoquinoline-1-carboxylato-k2N.O)cobalt(II) dihydrate. [Co(C10H6NO2)2(H2O)2 ]·2H2O. and trans-diaqua-bis (isoquinoline-1-carboxylato-k2N,O)nickel(II) dihydrate, [Ni- (C10H6NO2)2(H2 O)2]·2H2O, contain the same isoquinoline ligand, with both metal atoms residing on a centre of symmetry and having the same distorted octahedral coordination. In the former complex, the Co-O(water) bond length in the axial direction is 2.167 (2) A, which is longer than the Co-O(carboxylate) and Co-N bond lengths in the equatorial plane [2.055 (2) and 2.096 (2) A, respectively]. In the latter complex, the corresponding bond lengths for Ni-O (water). Ni-O(carboxylate) and Ni-N are 2.127 (2). 2.036 (2) and 2.039 (3) A. respectively. Both crystals are stabilized by similar stacking interactions of the ligand, and also by hydrogen bonds between the hydrate and coordinated water molecules.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1923N – PubChem