Tag: M.W=100-150

Melancon, Bruce J. published the artcileIsatin replacements applied to the highly selective, muscarinic M₁ PAM ML137: Continued optimization of an MLPCN probe molecule, Synthetic Route of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(2), 412-416, database is CAplus and MEDLINE.

This Letter describes the continued optimization of an MLPCN probe mol. I (ML137) with a focused effort on the replacement/modification of the isatin moiety present in this highly selective M₁ PAM. A diverse range of structures were validated as viable replacements for the isatin, many of which engendered sizeable improvements in their ability to enhance the potency and efficacy of acetylcholine when compared to ML137. Muscarinic receptor subtype selectivity for the M₁ receptor was also maintained.

Bioorganic & Medicinal Chemistry Letters published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Synthetic Route of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Reiberger, Robert published the artcileSynthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors, Synthetic Route of 724710-02-5, the publication is International Journal of Molecular Sciences (2021), 22(14), 7735, database is CAplus and MEDLINE.

The part of the influenza polymerase PA subunit featuring endonuclease activity is a target for anti-influenza therapies, including the FDA-approved drug Xofluza. A general feature of endonuclease inhibitors is their ability to chelate Mg²⁺ or Mn²⁺ ions located in the enzyme′s catalytic site. Previously, we screened a panel of flavonoids for PA inhibition and found luteolin and its C-glucoside orientin to be potent inhibitors. Through structural anal., we identified the presence of a 3′,4′-dihydroxyphenyl moiety as a crucial feature for sub-micromolar inhibitory activity. Here, we report results from a subsequent investigation exploring structural changes at the C-7 and C-8 positions of luteolin. Exptl. IC₅₀ values were determined by AlphaScreen technol. The most potent inhibitors were C-8 derivatives with inhibitory potencies comparable to that of luteolin. Bio-isosteric replacement of the C-7 hydroxyl moiety of luteolin led to a series of compounds with one-order-of-magnitude-lower inhibitory potencies. Using X-ray crystallog., we solved structures of the wild-type PA-N-terminal domain and its I38T mutant in complex with orientin at 1.9 Å and 2.2 Å resolution, resp.

International Journal of Molecular Sciences published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, Synthetic Route of 724710-02-5.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Teske, Kelly A. published the artcileParallel Chemistry Approach to Identify Novel Nuclear Receptor Ligands Based on the GW0742 Scaffold, SDS of cas: 763120-58-7, the publication is ACS Combinatorial Science (2017), 19(10), 646-656, database is CAplus and MEDLINE.

We describe the parallel synthesis of novel analogs of GW0742, a peroxisome proliferator-activated receptor δ (PPARδ) agonist. For that purpose, modified reaction conditions were applied, such as a solid-phase palladium-catalyzed Suzuki coupling. In addition, tetrazole-based compounds were generated as a bioisostere for carboxylic acid-containing ligand GW0742. The new compounds were investigated for their ability to activate PPARδ mediated transcription and their cross-reactivity with the vitamin D receptor (VDR), another member of the nuclear receptor superfamily. We identified many potent PPARδ agonists that were less toxic than GW0742, where ∼65 of the compounds synthesized exhibited partial PPARδ activity (23-98%) with EC₅₀ values ranging from 0.007-18.2 μM. Some ligands, such as compound 32, were more potent inhibitors of VDR-mediated transcription with significantly reduced PPARδ activity than GW0742, however, none of the ligands were completely selective for VDR inhibition over PPARδ activation of transcription.

ACS Combinatorial Science published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C2H4ClNO, SDS of cas: 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Arnold, Z. published the artcileSynthetic reactions of dimethylformamide. XVI. Formylalion of γ-picoline, SDS of cas: 19959-71-8, the publication is Collection of Czechoslovak Chemical Communications (1963), 863-8, database is CAplus.

cf. CA 59, 439h. Treatment of γ-picoline (I) with (Me₂NCH:NMe₂)⁺ClO₄^– (II) gave 4-(β-dimethylaminovinyl)pyridine (III) which reacted with IICONMe₂ (DMF) and COCl₂ to give α-(4-pyridyl)-β-dimethylaminoacrolein (IV), also obtained by treatment of I with DMF and COCl₂ or POCl₃. Alk. hydrolysis of IV afforded 4-pyridylmalonic dialdehyde (V). V with N₂H₄ gave 4-(4-pyridyl)pyrazole (VI), with H₂NCONHNH₂ (VII), 4-(4-pyridyl)pyrazole-1-carboxamide (VIII), with H₂NCSNHNH₂ (IX), α-(4-pyridyl)-β-thiosemicarbazinoacrolein (X), and with NH₃, 5-(4-pyridyl)pyrimidine (XI). To a mixture obtained from 0.26 g. Na and 100 ml. liquid NH₃, 1.86 g. I was added at -60°, followed, after 15 min., by 4 g. powd. II. After cooling and stirring for 15 addnl. min., the NH₃ was evaporated, the residue treated with 20 ml. C₆H₆ and 3 ml. H₂O, the aqueous layer extracted with C₆H₆, the extract washed with H₂O, dried, filtered, and evaporated to give 1.55 g. (52%) III, m. 101-2° (MeCOEt at -60°). Adding 1.5 g. III to a solution prepared by adding 5 ml. 3N COCl₂ in CHCl₃ to 3.65 g. DMF in 25 ml. CHCl₃, stirring the mixture 30 min. at room temperature, refluxing 6 hrs., treating with a saturated solution of K₂CO₃, extracting with 1:1 C₆H₆-EtOH, evaporating, and extracting the residue with C₆H₆ gave 1.4 g. (79%) IV, R_f 0.65 (Whatman Number 4 paper in MeCOEt-H₂O), m. 90-2° (MeCOEt at -70°), also obtained by adding 1.86 g. I to a reagent prepared from 21.9 g. DMF and 9.2 g. POCl₃, heating the mixture 6 hrs. at 70°, adding it to 70 ml. saturated solution of K₂CO₃ covered with 30 ml. 1:1 C₆H₆EtOH, filtering the salts, extracting the filtrate with the above mixture, drying the extract with anhydrous K₂CO₃, evaporating, extracting the residue with C₆H₆, and evaporating to dryness in vacuo, yield 3.2 g. (91%) crude, 2.4 g. (68%) pure. IV was also obtained in 51% yield by stirring a mixture of 0.93 g. I in 3 ml. CHCl₃, 7.3 g. DMF in 25 ml. CHCl₃, and 10 ml. 3N COCl₂ in CHCl₃ 1 hr. at room temperature and 5 hrs. at reflux. Heating 0.176 g. IV with 0.11 g. 50% KOH and a few drops H₂O to 70°, cooling the mixture, precipitating with concentrated KOH a potassium salt of V, filtering it off with suction, dissolving in H₂O, and acidifying the solution gave V, m. >320° (H₂O), also obtained in 80% yield by heating a mixture of 21.9 g. DMF, 9.2 g. POCl₃, and 1.86 g. I 6 hrs. at 70°, cooling, treating with 70 g. ice and a solution of 12 g. NaOH in 20 ml. H₂O at 20°, heating the mixture 10 min. at 90°, cooling, and acidifying with 1:1 HCl to pH 7. Treatment of 0.15 g. V with an equal amount of 90% N₂H₄ afforded VI, m. 198-9° (H₂O). Mixing a solution of 0.15 g. V in 6 ml. N HCl with a solution of 0.11 g. VII.HCl in 3 ml. N HCl gave VIII, m. 230°. Similar treatment of V with 0.09 g. IX gave X, m. 200°. Heating 0.3 g. V with 10 ml. NH₃ in EtOH 3 hrs. at 120° in a stainless steel autoclave, filtering the mixture with activated C, and evaporating in vacuo gave 0.12 g. XI, m. 107.5-8.5° (MeCOEt).

Collection of Czechoslovak Chemical Communications published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C8H7N3, SDS of cas: 19959-71-8.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

De Mendoza Sans, Javier published the artcileSynthesis of N-non-substituted 3(5)-hydrazino pyrazoles, Quality Control of 3553-12-6, the publication is Revista de la Real Academia de Ciencias Exactas, Fisicas y Naturales de Madrid (1971), 65(4), 739-839, database is CAplus.

A thesis with 68 references (5)-Amino-4-(ethoxycarbonyl)pyrazole (I) was hydrolyzed and decarboxylated to give 80% 3(5)-amino-pyrazole. I was diazotized and reduced to the corresponding hydrazine. Similarly I was diazotized and coupled to β-naphthol in base to give the asym-triazine (II).

Revista de la Real Academia de Ciencias Exactas, Fisicas y Naturales de Madrid published new progress about 3553-12-6. 3553-12-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Amide, name is 3-Acetamidopyrazole, and the molecular formula is C5H7N3O, Quality Control of 3553-12-6.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Graubaum, Heinz published the artcileAcyl migrations on 3(5)-aminopyrazole, Recommanded Product: 3-Acetamidopyrazole, the publication is Journal fuer Praktische Chemie/Chemiker-Zeitung (1993), 335(7), 585-8, database is CAplus.

3-Aminopyrazole forms 3 isomeric monoacylation products [I–III, R = Me, Et, Ph, 4-Me₂CHC₆H₄, 4-ClC₆H₄], 4 diacylation products and 3 triacylation products by reaction with RNCO. Acetamides IV [R¹ = RNHCO, R = Me, Et, Ph; R¹ = C(:NH)OR², R² = 4-MeOC₆H₄, 4-MeC₆H₄, 4-ClC₆H₄] were obtained from 3-acetylaminopyrazole and RNCO or R²OCN. Acyl migrations are observed depending on the reaction temperature and the structure of the acyl residue.

Journal fuer Praktische Chemie/Chemiker-Zeitung published new progress about 3553-12-6. 3553-12-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Amide, name is 3-Acetamidopyrazole, and the molecular formula is C5H7N3O, Recommanded Product: 3-Acetamidopyrazole.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Makisumi, Yasuo published the artcileAzaindolizine compounds. X. Synthesis of 5,7-disubstituted pyrazolo[1,5-a]pyrimidines, Safety of 3-Acetamidopyrazole, the publication is Chemical & Pharmaceutical Bulletin (1962), 612-20, database is CAplus.

cf. CA 57, 16606b. The title compounds (I) were prepared in general by condensing AcCH₂CO₂Et (II), CH₂Ac₂ (III), NCCH₂CO₂Et (IV), and CH₂(CO₂Et)₂ (V) separately with 5-amino-pyrazole (VI), its 1-Ph derivative (VII), its 4-EtO₂C derivative (VIII), and its 4-NC. derivative (IX). II kept overnight at room temperature with VI, VII, or VIII in the absence of solvent gave the corresponding 5-EtO₂CCH:CMeNH derivatives (X-XII) of pyrazole, m. 102°, 80-1°, and 175-6°, resp. On the other hand, refluxing II with VI or VIII 2-2.5 hrs. in AcOH gave the cyclized compounds (Ia, R = H and EtO₂C), m. 298-9° and 218-20°, resp., whereas refluxing II 4 hrs. with VII in AcOH gave the different cyclized compound (XIII), m. 188-9°. Ia (R = H and EtO₂C) and XIII were formed also by refluxing X-XII 2-3 hrs. with AcOH. Ia (R = EtO₂C) was also formed by refluxing XI 10 hrs. with Na in EtOH, and Ia (R = H) was prepared by refluxing VI 3 hrs. with II in EtOH containing anhydrous ZnCl₂. Hydrolysis of 0.5 g. Ia (R = EtO₂C) by heating 2 hrs. on a steam bath with 10% NaOH yielded 0.45 g. corresponding free acid, m. 296-7° (decomposition), and this (0.5 g.) was successfully decarboxylated by refluxing 3 hrs. with 40% H₂SO₄ to yield 0.32 g. Ia (R = H). Also, 0.94 g. IX refluxed 2.5 hrs. with II in AcOH yielded 1.5 g. Ia (R = cyano), m. 313° (decomposition), and this (0.5 g.) hydrolyzed and decarboxylated by refluxing 4 hrs. with 40% H₂SO₄ also yielded 0.4 g. Ia (R = H). Refluxing III (in place of II) with VI or VIII 10-12 hrs. in EtOH containing 3 drops piperidine, removing the solvent, and purifying the residue by Al₂O₃ chromatography gave, resp., Ib (R = H), m. 40-40.5°, and Ib (R = EtO₂C), m. 107-7.5°. The latter, like Ia (R = EtO₂C) was hydrolyzed to the corresponding free acid, m. 178-9°, which was decarboxylated either by heating 20 min. at 200° without solvent or by refluxing with 40% H₂SO₄ to give Ib (R = H), formed likewise by refluxing the ester, Ib (R = EtO₂C), itself with 40% H₂SO₄. Use of IV (in place of II or III) with VI or VIII in EtOH containing Na gave, resp., Ic (R = H), m. 306° (decomposition), and Ic (R = EtO₂C), m. 236-7°, which was hydrolyzed to the free acid, m. 296° (decomposition), and this was decarboxylated by heating in vacuo at 260-70° to give Ic (R = H). However, heating IV with VI 2 hrs. at 160-70° in the absence of solvent gave the noncyclized 5-(2-cyanoacetamido)-pyrazole (XVI), m. 211-12° (decomposition), and this was cyclized to Ic (R = H) by heating 5 hrs. on a steam bath in AcOH. Finally, V (in place of II) with VI or VIII in EtOH containing Na gave, resp., Id (R = H), m. 239-40° (decomposition), and Id (R = EtO₂C), m. 186-7° (decomposition), which also was hydrolyzed to the corresponding acid, m. 229° (decomposition), and this heated 5 min. at 235° was not only decarboxylated but also decomposed to give 5-acetamidopyrazole (XV), m. 223-4°, identical with the product obtained by refluxing VI 1 hr. with AcOH. However, heating VI 15 min. on a steam bath with Ac₂O gave 1-acetyl-5-acetamidopyrazole, m. 190.5-1.5°, which was readily converted to XV by heating with H₂O. In support of the structures, ultraviolet absorption curves were shown for Ia (R = H, EtO₂C, and CN), X-XII, Ic (R = H), Id (R = H), XIV, and XV, and both infrared and ultraviolet absorption data were reported for most of the compounds The infrared spectra of I showed that the 5- or 7-HO groups were mainly in the lactam form, whereas the 5- or 7-H₂N groups kept the amino form in neutral medium, thus showing analogy with pyrimidine derivatives

Chemical & Pharmaceutical Bulletin published new progress about 3553-12-6. 3553-12-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Amide, name is 3-Acetamidopyrazole, and the molecular formula is C5H7N3O, Safety of 3-Acetamidopyrazole.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Sun, Shaoyi published the artcileSystematic evaluation of amide bioisosteres leading to the discovery of novel and potent thiazolylimidazolidinone inhibitors of SCD1 for the treatment of metabolic diseases, Name: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(2), 520-525, database is CAplus and MEDLINE.

Several five- and six-membered heterocycles were introduced to replace the C2-position amide bond of the original 2-aminothiazole-based hit compound Specifically, replacement of the amide bond with an imidazolidinone moiety yielded a novel and potent thiazolylimidazolidinone series of SCD1 inhibitors. XEN723 I was identified after optimization of the thiazolylimidazolidinone series. This compound demonstrated a 560-fold improvement in in vitro potency and reduced plasma desaturation indexes in a dose dependent manner, with an EC₅₀ of 4.5 mg/kg.

Bioorganic & Medicinal Chemistry Letters published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C15H14Cl2S2, Name: 1H-Pyrazole-4-boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Ran, Xu published the artcileStructure-Based Design of γ-Carboline Analogues as Potent and Specific BET Bromodomain Inhibitors, Computed Properties of 763120-58-7, the publication is Journal of Medicinal Chemistry (2015), 58(12), 4927-4939, database is CAplus and MEDLINE.

Small-mol. inhibitors of bromodomain and extra terminal proteins (BET), including BRD2, BRD3, and BRD4 proteins have therapeutic potential for the treatment of human cancers and other diseases and conditions. In this paper, the authors report the design, synthesis, and evaluation of γ-carboline-containing compounds as a new class of small-mol. BET inhibitors. The most potent inhibitor I (RX-37) obtained from this study binds to BET bromodomain proteins (BRD2, BRD3, and BRD4) with K_i values of 3.2-24.7 nM and demonstrates high selectivity over other non-BET bromodomain-containing proteins. Compound I potently and selectively inhibits cell growth in human acute leukemia cell lines harboring the rearranged mixed lineage leukemia 1 gene. The authors have determined a cocrystal structure of I in complex with BRD4 BD2 at 1.4 Å resolution, which provides a solid structural basis for the compound’s high binding affinity and for its further structure-based optimization. Compound I represents a promising lead compound for the development of a new class of therapeutics for the treatment of human cancer and other conditions.

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Computed Properties of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Yang, Yong published the artcileImpact of Boronate Capping Groups on Biological Characteristics of Novel ^99mTc(III) Complexes [^99mTcCl(CDO)(CDOH)₂B-R] (CDOH₂ = Cyclohexanedione Dioxime), Recommanded Product: (1H-Pyrazol-5-yl)boronic acid, the publication is Bioconjugate Chemistry (2015), 26(2), 316-328, database is CAplus and MEDLINE.

This study sought to explore the impact of boronate groups on the heart uptake and myocardial retention of novel ^99mTc(III) complexes [^99mTcCl(CDO)(CDOH)₂B-R] (^99mTc-ISboroxime: R = isoxazol-4-yl (IS); ^99mTc-MPboroxime: R = N-methylpyridinium (MP); ^99mTc-PAboroxime: R = pyrazol-3-yl (PA); ^99mTc-PYboroxime: R = pyridin-3-yl (PY); and ^99mTc-5Uboroxime: R = uracil-5-yl (5U)). All five new ^99mTc(III) radiotracers were prepared in high yield and high radiochem. purity (RCP = 90-98%), and they remained stable in the kit mixture for >6 h. Biodistribution and imaging (planar and SPECT) studies were carried out using Sprague-Dawley (SD) rats. Planar image quantification was performed to compare their myocardial retention and liver clearance kinetics. It was found that their heart retention and liver clearance curves were best fitted to the biexponential decay function. The initial heart uptake at 0-1 min after injection followed the general ranking order of ^99mTc-ISboroxime (4.98 ± 1.05%ID) ∼ ^99mTc-Teboroxime (4.56 ± 0.91%ID) ∼ ^99mTc-PAboroxime (4.03 ± 1.23%ID) ∼ ^99mTc-PYboroxime (4.07 ± 0.80%ID) > ^99mTc-5Uboroxime (3.24 ± 0.67%ID) > ^99mTc-MPboroxime (2.53 ± 0.65%ID). The fast-phase myocardial retention time followed the general order of ^99mTc-PAboroxime (3.21 ± 0.29 min) > ^99mTc-Teboroxime (1.63 ± 0.40 min) ∼ ^99mTc-PYboroxime (1.57 ± 0.29 min) ∼ ^99mTc-ISboroxime (1.55 ± 0.32 min) > ^99mTc-MPboroxime (0.68 ± 0.16 min) > ^99mTc-5Uboroxime (0.33 ± 0.11 min). ^99mTc-PAboroxime (3.05 ± 1.10%ID/g) and ^99mTc-ISboroxime (3.75 ± 0.68%ID/g) had the 2 min initial heart uptake very close to that of ^99mTc-Teboroxime (3.30 ± 0.50%ID/g). However, the myocardial retention time of ^99mTc-PAboroxime was significantly longer than that of ^99mTc-ISboroxime and ^99mTc-Teboroxime. Even though the best time window is 0-5 min for SPECT image acquisition, high quality SPECT images could be obtained during the first 30 min postinjection of ^99mTc-PAboroxime in SD rats. This statement was supported by the SPECT/CT studies in normal pigs. On the basis of results from this study, it was concluded that boronate groups had significant impact on the heart uptake, myocardial retention, and liver clearance kinetics of ^99mTc(III) complexes [^99mTcCl(CDO)(CDOH)₂B-R]. The combination of high initial heart uptake with longer myocardial retention makes it possible to image the heart with ^99mTc-PAboroxime during the first 30 min using both standard and specialized cardiac SPECT cameras.

Bioconjugate Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C7H3IN2O2, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics