Month: December 2022

Schenck Eidam, Hilary published the artcileDiscovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS, HPLC of Formula: 76283-09-5, the publication is ACS Medicinal Chemistry Letters (2018), 9(7), 623-628, database is CAplus and MEDLINE.

Abdominal pain and abnormal bowel habits represent major symptoms for irritable bowel syndrome (IBS) patients that are not adequately managed. Although the etiol. of IBS is not completely understood, many of the functions of the gastrointestinal (GI) tract are regulated by the enteric nervous system (ENS). Inflammation or stress-induced expression of growth factors or cytokines may lead to hyperinnervation of visceral afferent neurons in GI tract and contribute to the pathophysiol. of IBS. Rearranged during transfection (RET) is a neuronal growth factor receptor tyrosine kinase critical for the development of the ENS as exemplified by Hirschsprung patients who carry RET loss-of-function mutations and lack normal colonic innervation leading to colonic obstruction. Similarly, RET signaling in the adult ENS maintains neuronal function by contributing to synaptic formation, signal transmission, and neuronal plasticity. Inhibition of RET in the ENS represents a novel therapeutic strategy for the normalization of neuronal function and the symptoms of IBS patients. Herein, we describe our screening effort and subsequent structure-activity relationships (SARs) in optimizing potency, selectivity, and mutagenicity of the series, which led to the discovery of a first-in-class, gut-restricted RET kinase inhibitor, 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide (15, GSK3179106), as a clin. candidate for the treatment of IBS. GSK3179106 is a potent, selective, and gut-restricted pyridone hinge binder small mol. RET kinase inhibitor with a RET IC₅₀ of 0.3 nM and is efficacious in vivo.

ACS Medicinal Chemistry Letters published new progress about 76283-09-5. 76283-09-5 belongs to bromides-buliding-blocks, auxiliary class Fluoride,Bromide,Benzyl bromide,Benzene, name is 4-Bromo-1-(bromomethyl)-2-fluorobenzene, and the molecular formula is C7H5Br2F, HPLC of Formula: 76283-09-5.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Ullrich, K. J. published the artcileBisubstrates: Substances that interact with renal contraluminal organic anion and organic cation transport systems. I. Amines, piperidines, piperazines, azepines, pyridines, quinolines, imidazoles, thiazoles, guanidines and hydrazines, Application of Dimidium bromide, the publication is Pfluegers Archiv (1993), 425(3-4), 280-99, database is CAplus and MEDLINE.

The authors examined the renal transport of nine classes of N-containing substances by the contraluminal organic anion (p-amminohippurate) and contraluminal organic cation (N’-methylnicotinamide and tetra-Et ammonium) transport systems. Many substrates interacted with both systems if they were sufficiently hydrophobic and had groups that were sufficiently electron-attracting.

Pfluegers Archiv published new progress about 518-67-2. 518-67-2 belongs to bromides-buliding-blocks, auxiliary class Other Aromatic Heterocyclic,Salt,Amine,Benzene, name is Dimidium bromide, and the molecular formula is C12H14O2, Application of Dimidium bromide.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Jardine, F. H. published the artcileChemistry of copper(I) complexes. I. Halo-complexes, Related Products of bromides-buliding-blocks, the publication is Journal of the Chemical Society [Section] A: Inorganic, Physical, Theoretical (1970), 238-40, database is CAplus.

A new method of preparing halocopper(I) complexes by using tertiary phosphines as ligands and reducing agents is described. The complexes prepared have been treated with various mono- and bidentate ligands and structures assigned to the derivatives on the basis of their phys. properties. The complexes prepared were: Cu X(PPh3)3, where X = F, Cl, Br; [Cu XPR3]4, where X = Cl, Br and R = Ph, X = Cl and R = Et; Cu X(PPh3)L, where X = Br, Cl, I and L = pyridine, γ- and β-picoline, 2,2′-bipyridyl, 1,10-phenanthroline (phen), or 2,2′-biquinolyl (biquin); CuI(PBu3)L and [CuIL]2, where L = phen or biquin; and [Cu(phen)2]I.

Journal of the Chemical Society [Section] A: Inorganic, Physical, Theoretical published new progress about 25753-84-8. 25753-84-8 belongs to bromides-buliding-blocks, auxiliary class Copper, name is Bromo(1,10-phenanthroline)(triphenylphosphine)copper(I), and the molecular formula is C30H24BrCuN2P, Related Products of bromides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Garcia Suarez, Eduardo J. published the artcileNew alkyl derivatives phosphine sulfonate (P-O) ligands. Catalytic activity in Pd-catalysed Suzuki-Miyaura reactions in water, Name: Sodium 3-bromopropane-1-sulfonate, the publication is Dalton Transactions (2007), 2859-2861, database is CAplus and MEDLINE.

Novel phosphine-alkanesulfonate P-O-chelate ligands and their palladium complexes were prepared; the complexes exhibit excellent catalytic activity in Suzuki-Miyaura coupling of aryl bromides and moderate activity in coupling of aryl chlorides with arylboronic acids. Reaction of (2-MeOC₆H₄)₂PLi with Br(CH₂)_nSO₃Na gave bidentate phosphinosulfonates (2-MeOC₆H₄)₂P(CH₂)_nSO₃H (1, 2; n = 2, 3). Complexation of 1 with [Pd₂(μ-Cl)₂(η¹,η²-C₈H₁₃OMe)₂] gave the palladium(II) complex, [Pd(η¹,η²-C₈H₁₃OMe)[(2-MeOC₆H₄)₂P(CH₂)_nSO₃-κO,κP]] (1a, C₈H₁₃OMe = 6-methoxy-1-cycloocten-5-yl), which structure was confirmed by x-ray diffraction anal. Suzuki-Miyaura coupling of R¹Br with R²B(OH)₂ catalyzed by Pd(OAc)₂/L (L = 1, 2) gave the corresponding biaryls R¹R² (R¹ = 4MeCOC₆H₄, Ph, 4-MeOC₆H₄; R² = Ph, 1-naphthyl, 4-FC₆H₄, 4-MeOC₆H₄) with >99% yields. The ligands 1 and 2 are air-stable as well as water soluble; the coupling reactions were run in neat water and under microwave heating as well.

Dalton Transactions published new progress about 55788-44-8. 55788-44-8 belongs to bromides-buliding-blocks, auxiliary class Bromide,Salt,Aliphatic hydrocarbon chain,Aliphatic hydrocarbon chain, name is Sodium 3-bromopropane-1-sulfonate, and the molecular formula is C3H6BrNaO3S, Name: Sodium 3-bromopropane-1-sulfonate.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Kumar, H. C. Sampath published the artcileSynthesis And Third-order Nonlinear Optical Studies of Four-Coordinated Copper(I) Complexes, HPLC of Formula: 25753-84-8, the publication is AIP Conference Proceedings (2011), 671-673, database is CAplus.

Three Cu(I) halide complexes [Cu(L)(PPh₃)X] (L = 1,10-phenanthroline, X = Cl (1), Br (2) and I (3), PPh₃ = triphenylphosphine) have been synthesized and characterized by spectroscopic techniques. Further structure of the complex 1 was confirmed by single crystal X-ray diffraction anal. The nonlinear optical properties of the complexes were investigated at 532 nm using single beam Z-scan technique with nanosecond laser pulses. The complexes showed strong optical limiting behavior due to effective three-photon absorption (3PA). The values of 3PA coefficients (γ) for 1, 2 and 3 were found to be 3.2×10^-24 m³/W², 6.0×10^-25 m³/W² and 1.2×10^-23 m³/W² resp., which are comparable to good optical limiting materials. These studies demonstrate that the Ligand copper coordinative bonds facilitate the polarization of the electronic π-system which optimizes the third-order NLO response in the reported complexes. (c) 2011 American Institute of Physics.

AIP Conference Proceedings published new progress about 25753-84-8. 25753-84-8 belongs to bromides-buliding-blocks, auxiliary class Copper, name is Bromo(1,10-phenanthroline)(triphenylphosphine)copper(I), and the molecular formula is C30H24BrCuN2P, HPLC of Formula: 25753-84-8.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Trost, Barry M. published the artcileRuthenium-Catalyzed Cycloisomerizations of Diynols, Category: bromides-buliding-blocks, the publication is Journal of the American Chemical Society (2005), 127(13), 4763-4776, database is CAplus and MEDLINE.

A wide variety of diynols containing tertiary, secondary, and primary propargylic alcs. undergo a cycloisomerization reaction to form dienones and dienals in the presence of a catalytic amount of [CpRu(CH₃CN)₃]PF₆. The formation of five- and six-membered rings is possible using this methodol. E.g., [CpRu(CH₃CN)₃]PF₆ catalyzed the cycloisomerization of diynol I to give 45% dienal II. Secondary diynols react to form single geometrical isomeric dienones and dienals. Primary diynols undergo a cycloisomerization as well as a hydrative cyclization process. The utility of primary diynol cycloisomerization is demonstrated in a synthesis of (+)-α-kainic acid.

Journal of the American Chemical Society published new progress about 69361-41-7. 69361-41-7 belongs to bromides-buliding-blocks, auxiliary class PROTAC Linker,Aliphatic Linker, name is (4-Bromobut-1-yn-1-yl)trimethylsilane, and the molecular formula is C12H12F3N5O2, Category: bromides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Iyer, Malliga R. published the artcileProbes for narcotic receptor mediated phenomena. N-substituted rac-cis-4a-arylalkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols, Synthetic Route of 1997-80-4, the publication is European Journal of Medicinal Chemistry (2015), 531-539, database is CAplus and MEDLINE.

Racemic N-substituted -1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols containing cis-4a-aralkyl groups were explored as probes for opioid receptors. Specifically cis-4a-phenylpropyl, -phenylbutyl, and-phenylpentyl groups coupled with widely varied substituents on the nitrogen atom were synthesized and their pharmacol. profiles at opioid receptors examined The study yielded compounds with good affinity and moderate to potent antagonist activity at the μ- and δ-opioid receptors, and agonist activity at the κ-opioid receptor. An N-allyl substituent in the C4a phenylpropyl series induced 6-fold higher affinity at δ-than μ-receptors, while an N-CPM substituent in the C4a (CH₂)₃Ph series led to a compound with high δ-affinity and potent δ-antagonist activity.

European Journal of Medicinal Chemistry published new progress about 1997-80-4. 1997-80-4 belongs to bromides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Bromide,Benzene, name is 1-(2-Bromoethyl)-3-(trifluoromethyl)benzene, and the molecular formula is C9H8BrF3, Synthetic Route of 1997-80-4.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Iyer, Malliga R. published the artcileProbes for narcotic receptor mediated phenomena. 47.¹ Novel C4a- and N-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols, Safety of 1-(2-Bromoethyl)-3-(trifluoromethyl)benzene, the publication is Bioorganic & Medicinal Chemistry (2013), 21(11), 3298-3309, database is CAplus and MEDLINE.

A series of N-Me rac-cis-4a-aralkyl- and alkyl-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols have been prepared using a simple previously designed synthetic route, to find a ligand that would interact with both μ- and δ-opioid receptors. A C4a-phenethyl derivative I, was found to have modest receptor affinity both at μ- (K_i = 60 nM) and δ-opioid receptors (K_i = 64 nM). The N-Me substituent of I and that of other ligands in the series was then modified to obtain compounds with different N-substituents that might provide higher affinity at both receptors. A number of compounds differently substituted at C4a and N were synthesized and evaluated. Binding studies and functional assays revealed a moderately selective δ-antagonist, selective μ-δ antagonists, and a μ-κ antagonist.

Bioorganic & Medicinal Chemistry published new progress about 1997-80-4. 1997-80-4 belongs to bromides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Bromide,Benzene, name is 1-(2-Bromoethyl)-3-(trifluoromethyl)benzene, and the molecular formula is C9H8BrF3, Safety of 1-(2-Bromoethyl)-3-(trifluoromethyl)benzene.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Ellermann, Joachim published the artcileMethyl-coenzyme-M reductase from Methanobacterium thermoautotrophicum (strain Marburg). Purity, activity and novel inhibitors, Category: bromides-buliding-blocks, the publication is European Journal of Biochemistry (1989), 184(1), 63-8, database is CAplus and MEDLINE.

Methyl-coenzyme-M reductase from M. thermoautotrophicum (strain Marburg) was purified to a stage where, besides the α, β and γ subunits, no addnl. polypeptides were detectable in the preparation Under appropriate conditions the enzyme was found to catalyze the reduction of methyl-CoM with 7-mercaptoheptanoylthreonine phosphate (H-S-HTP) to CH₄ at a specific rate of 2.5 μmol min^-1 mg protein^-1. This finding contradicts a recent report that methyl-CoM reductase is only active when some contaminating proteins are present. The 2 polypeptides encoded by the open reading frames ORF₁ and ORF₂ of the methyl-CoM reductase transcription unit did not copurify with the α, β and γ subunits. They were neither required nor did they stimulate the activity under the assay conditions. 3-Bromopropanesulfonate (apparent K_i = 0.05 μM) and 2-azidoethanesulfonate (apparent K_i = 1 μM) were found to be 2 new competitive inhibitors of methyl-CoM reductase. Both inhibitors were considerably more effective than the classical 2-bromoethanesulfonate (apparent K_i = 4 μM).

European Journal of Biochemistry published new progress about 55788-44-8. 55788-44-8 belongs to bromides-buliding-blocks, auxiliary class Bromide,Salt,Aliphatic hydrocarbon chain,Aliphatic hydrocarbon chain, name is Sodium 3-bromopropane-1-sulfonate, and the molecular formula is C3H6BrNaO3S, Category: bromides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary

Lawson, Kenneth V. published the artcileSynthesis of a designed sesquiterpenoid that forms useful composites with peptides and related oligomers, Category: bromides-buliding-blocks, the publication is Tetrahedron Letters (2011), 52(6), 653-654, database is CAplus.

Efficient desymmetrization of isophthalaldehyde allows a scalable asym. synthesis of cinnamylated sesquiterpenoid I. We have shown that I forms useful, property-altered composites with peptides and related oligomers. The current synthesis promises to expand those efforts considerably.

Tetrahedron Letters published new progress about 69361-41-7. 69361-41-7 belongs to bromides-buliding-blocks, auxiliary class PROTAC Linker,Aliphatic Linker, name is (4-Bromobut-1-yn-1-yl)trimethylsilane, and the molecular formula is C7H13BrSi, Category: bromides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary