Tag: M.W=100-150

Schroeder, Tenna Juul published the artcileThe identification of AF38469: An orally bioavailable inhibitor of the VPS10P family sorting receptor Sortilin, Recommanded Product: 4-Amino-2-picoline, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(1), 177-180, database is CAplus and MEDLINE.

The identification of the novel, selective, orally bioavailable sortilin inhibitor AF38469 [5-(trifluoromethyl)-2- [(6-methylpyridin-2-ylamino)carbonyl]]benzoic acid is described. Structure-activity relationships and syntheses are reported, along with an X-ray crystal structure of the sortilin-AF38469 protein-inhibitor complex.

Bioorganic & Medicinal Chemistry Letters published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Recommanded Product: 4-Amino-2-picoline.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Dick, Benjamin L. published the artcileMetal-Binding Isosteres as New Scaffolds for Metalloenzyme Inhibitors, SDS of cas: 197958-29-5, the publication is Inorganic Chemistry (2018), 57(15), 9538-9543, database is CAplus and MEDLINE.

The principle of isosteres or bioisosteres in medicinal chem. is a central and essential concept in modern drug discovery. For example, carboxylic acids are often replaced by bioisosteres to mitigate issues related to lipophilicity or acidity while retaining acidic characteristics in addition to hydrogen bond donor/acceptor abilities. Sep., the development of metal-binding pharmacophores (MBPs) for binding to the active site metal ion in metalloenzymes of therapeutic interest is an emerging area in the realm of fragment-based drug discovery (FBDD). The direct application of the bioisostere concept to MBPs has not been well-described or systematically investigated. Herein, the picolinic acid MBP is used as a case study for the development of MBP isosteres (so-called MBIs). Many of these isosteres are novel compounds, and data on their physicochem. properties, metal binding capacity, and metalloenzyme inhibition characteristics are presented. The results show that MBIs of picolinic acid generally retain metal coordinating properties and exhibit predictable metalloenzyme inhibitory activity while possessing a broad range of physicochem. properties (e.g., pK_a, logP). These findings demonstrate the use of bioisosteres results in an untapped source of metal binding functional groups suitable for metalloenzyme FBDD. These MBIs provide a previously unexplored route for modulating the physicochem. properties of metalloenzyme inhibitors and improving their drug-likeness.

Inorganic Chemistry published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, SDS of cas: 197958-29-5.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Whitlock, Gavin A. published the artcileNovel 2-imidazoles as potent and selective α_1A adrenoceptor partial agonists, Safety of 2-Pyridinylboronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(9), 2930-2934, database is CAplus and MEDLINE.

Novel 2-imidazoles have been identified as potent partial agonists of the α_1A adrenergic receptor, with good selectivity over the α_1B, α_1D and α_2A receptor sub-types. Sulfonamide 23 (I) possessed attractive drug-like properties with respect to physicochem. and ADME properties and wide ligand selectivity.

Bioorganic & Medicinal Chemistry Letters published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C17H14N2O2, Safety of 2-Pyridinylboronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Dumas, Megan E. published the artcileDual inhibition of Kif15 by oxindole and quinazolinedione chemical probes, Category: pyridine-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(2), 148-154, database is CAplus and MEDLINE.

The mitotic spindle is a microtubule-based machine that segregates a replicated set of chromosomes during cell division. Many cancer drugs alter or disrupt the microtubules that form the mitotic spindle. Microtubule-dependent mol. motors that function during mitosis are logical alternative mitotic targets for drug development. Eg5 (Kinesin-5) and Kif15 (Kinesin-12), in particular, are an attractive pair of motor proteins, as they work in concert to drive centrosome separation and promote spindle bipolarity. Furthermore, we hypothesize that the clin. failure of Eg5 inhibitors may be (in part) due to compensation by Kif15. In order to test this idea, we screened a small library of kinase inhibitors and identified GW108X, an oxindole that inhibits Kif15 in vitro. We show that GW108X has a distinct mechanism of action compared with a com. available Kif15 inhibitor, Kif15-IN-1 and may serve as a lead with which to further develop Kif15 inhibitors as clin. relevant agents.

Bioorganic & Medicinal Chemistry Letters published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Blake, James F. published the artcileDiscovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development, HPLC of Formula: 18437-58-6, the publication is Journal of Medicinal Chemistry (2016), 59(12), 5650-5660, database is CAplus and MEDLINE.

The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clin., resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Described herein is the discovery and characterization of GDC-0994 (22), an orally bioavailable small mol. inhibitor selective for ERK kinase activity.

Journal of Medicinal Chemistry published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, HPLC of Formula: 18437-58-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Wu, Wen-Lian published the artcileDesign and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists, Safety of (6-Hydroxypyridin-3-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2006), 16(14), 3674-3678, database is CAplus and MEDLINE.

Biaryl urea lead compound I was discovered earlier in an MCH antagonist program. Novel benzimidazole analogs with increased chem. stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model.

Bioorganic & Medicinal Chemistry Letters published new progress about 903899-13-8. 903899-13-8 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester,Alcohol,Boronic Acids,Boronic acid and ester, name is (6-Hydroxypyridin-3-yl)boronic acid, and the molecular formula is C2H8Cl2N4S2, Safety of (6-Hydroxypyridin-3-yl)boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

van Veldhoven, Jacobus P. D. published the artcileTargeting the K_v11.1 (hERG) channel with allosteric modulators. Synthesis and biological evaluation of three novel series of LUF7346 derivatives, Computed Properties of 18437-58-6, the publication is European Journal of Medicinal Chemistry (2021), 113033, database is CAplus and MEDLINE.

Three novel series of substituted benzophenones for their allosteric modulation of the human Kv11.1 (hERG) channel were synthesized and evaluated. Effects of this is compared with reference compound LUF7346 previously shown to shorten the action potential of cardiomyocytes derived from human stem cells. Most compounds behaved as neg. allosteric modulators (NAMs) of [3H]dofetilide binding to the channel. Compound III [R = 2-Cl; R¹ = CH₂cPr; X= Y = C] was the most potent amongst all ligands, remarkably reducing the affinity of dofetilide in competitive displacement assays. One of the other II [R = H; X = N] tested in a second radioligand binding set-up, displayed unusual displacement characteristics with a pseudo-Hill coefficient significantly distinct from unity, further indicative of its allosteric effects on the channel. Some compounds were evaluated in a more physiol. relevant context in beating cardiomyocytes derived from human induced pluripotent stem cells. Surprisingly, the compounds tested showed effects quite different from the reference NAM LUF7346. For instance, compound I [R = 3-Me] prolonged, rather than shortened, the field potential duration, while it did not influence this parameter when the field potential was already prolonged by dofetilide. In subsequent patch clamp studies on HEK293 cells expressing the hERG channel the compounds behaved as channel blockers. In conclusion, new allosteric modulators of the hERG channel were successfully synthesized and identified . Unexpectedly, their effects differed from the reference compound in functional assays on hERG-HEK293 cells and human cardiomyocytes, to the extent that the compounds behaved as stand-alone channel blockers.

European Journal of Medicinal Chemistry published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C7H8BClO2, Computed Properties of 18437-58-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Guckian, Kevin published the artcilePyrazolone based TGFβR1 kinase inhibitors, Category: pyridine-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(1), 326-329, database is CAplus and MEDLINE.

Interruption of TGFβ signaling through inhibition of the TGFβR1 kinase domain may prove to have beneficial effect in both fibrotic and oncol. diseases. Herein we describe the SAR of a novel series of TGFβR1 kinase inhibitors containing a pyrazolone core. Most TGFβR1 kinase inhibitors described to date contain a core five-membered ring bearing N as H-bond acceptor. Described herein is a novel strategy to replace the core structure with pyrazolone ring, in which the carbonyl group is designed as an H-bond acceptor to interact with catalytic Lys 232.

Bioorganic & Medicinal Chemistry Letters published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Dardir, Amira H. published the artcileSynthesis of Triarylmethanes via Palladium-Catalyzed Suzuki-Miyaura Reactions of Diarylmethyl Esters, Category: pyridine-derivatives, the publication is Organometallics (2021), 40(14), 2332-2344, database is CAplus and MEDLINE.

The synthesis of triarylmethanes via Pd-catalyzed Suzuki-Miyaura reactions between diarylmethyl 2,3,4,5,6-pentafluorobenzoates and aryl boronic acids is described. The system operates under mild conditions and has a broad substrate scope, including the coupling of diphenylmethanol derivatives that do not contain extended aromatic substituents. This is significant as these substrates, which result in the types of triarylmethane products that are prevalent in pharmaceuticals, have not previously been compatible with systems for diarylmethyl ester coupling. Also, the reaction can be performed stereospecifically to generate stereoinverted products. From DFT calculations, probably the oxidative addition of the diarylmethyl 2,3,4,5,6-pentafluorobenzoate substrate occurs via an S_N2 pathway, which results in the inverted products. Mechanistic studies indicate that oxidative addition of the diarylmethyl 2,3,4,5,6-pentafluorobenzoate substrates to (IPr)Pd(0) results in the selective cleavage of the O-C(benzyl) bond in part because of a stabilizing η³-interaction between the benzyl ligand and Pd. This is in contrast to previously described Pd-catalyzed Suzuki-Miyaura reactions involving Ph esters, which involve selective cleavage of the C(acyl)-O bond, because there is no stabilizing η³-interaction. It is anticipated that this fundamental knowledge will aid the development of new catalytic systems, which use esters as electrophiles in cross-coupling reactions.

Organometallics published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Kuduk, Scott D. published the artcileQuinolizidinone Carboxylic Acids as CNS Penetrant, Selective M₁ Allosteric Muscarinic Receptor Modulators, Safety of 2-Pyridinylboronic acid, the publication is ACS Medicinal Chemistry Letters (2010), 1(6), 263-267, database is CAplus and MEDLINE.

Pos. allosteric modulation of the M₁ muscarinic receptor represents an approach to treat the cognitive decline in patients with Alzheimer’s disease. Replacement of a quinolone ring system in a quinolone carboxylic acid series of M₁ modulators with a quinolizidinone bearing a basic amine linkage led to a series of compounds with higher free fraction, enhanced CNS exposure, and improved efficacy in rodent in vivo models of cognition.

ACS Medicinal Chemistry Letters published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Safety of 2-Pyridinylboronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem