Category: 1003-32-3

O’Connor, Stephen J.; Barr, Kenneth J.; Wang, Le; Sorensen, Bryan K.; Tasker, Andrew S.; Sham, Hing; Ng, Shi-Chung; Cohen, Jerome; Devine, Edward; Cherian, Sajeev; Saeed, Badr; Zhang, Haichao; Lee, Jang Yun; Warner, Robert; Tahir, Stephen; Kovar, Peter; Ewing, Patricia; Alder, Jeffrey; Mitten, Michael; Leal, Juan; Marsh, Kennan; Bauch, Joy; Hoffman, Daniel J.; Sebti, Said M.; Rosenberg, Saul H. published the artcile< Second-Generation Peptidomimetic Inhibitors of Protein Farnesyltransferase Demonstrating Improved Cellular Potency and Significant in Vivo Efficacy>, COA of Formula: C4H3NOS, the main research area is peptidomimetic preparation protein farnesyltransferase inhibitor antitumor; protein farnesyltransferase inhibitor peptidomimetic structure antitumor; antitumor agent peptidomimetic protein farnesyltransferase inhibitor.

The synthesis and evaluation of analogs of previously reported farnesyltransferase inhibitors, a pyridyl benzyl ether and a pyridylbenzylamine, are described. Substitution of the pyridyl benzyl ether at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of the pyridylbenzylamine at the benzyl nitrogen yielded 4-(N-benzyl-N-3-pyridylaminomethyl)-2-(2-methylphenyl)benzoylmethionine (I), which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 4-(N-3,5-difluorobenzyl-N-phenylaminomethyl)-2-(2-methylphenyl)benzoylmethionine, which demonstrated a dramatically improved pharmacokinetic profile. I and 4-(N-benzyl-N-phenylaminomethyl)-2-(2-methylphenyl)benzoylmethionine demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, COA of Formula: C4H3NOS.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Scholz, Marek; Dedic, Roman; Miguel, Miriam; Lavilla, Rodolfo; Nonell, Santi published the artcile< Thiazolyl-substituted porphyrins as standards for singlet molecular oxygen photosensitization>, Category: thiazole, the main research area is thiazolyl substituted porphyrin derivative photophys singlet mol oxygen photosensitization.

Thiazolyl- and bithiazolyl-substituted porphyrins have been characterized to assess their potential as new standards for singlet mol. oxygen photosensitization. Their absorption, fluorescence, phosphorescence and triplet-triplet spectra are slightly red-shifted relative to those of tetraphenylporphine (TPP), a well-established singlet mol. oxygen standard Likewise, the singlet and triplet lifetimes, as well as the fluorescence quantum yields are roughly one order of magnitude smaller than those of TPP, while the triplet and singlet oxygen quantum yields increase concomitantly to ca. 1.

Journal of Porphyrins and Phthalocyanines published new progress about Delayed fluorescence. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Category: thiazole.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Kobayashi, Naotake; Sato, Norihito; Fujimura, Yuko; Kihara, Tsuyoshi; Sugita, Katsuji; Takahashi, Kouji; Koike, Katsumi; Sugawara, Tamio; Tada, Yukio; Nakai, Hiroshi; Yoshikawa, Takayoshi published the artcile< Discovery of the Orally Effective Thyrotropin-Releasing Hormone Mimetic: 1-{N-[(4S,5S)-(5-Methyl-2-oxooxazolidine-4-yl)carbonyl]-3-(thiazol-4-yl)-L-alanyl}-(2R)-2-methylpyrrolidine Trihydrate (Rovatirelin Hydrate)>, Computed Properties of 1003-32-3, the main research area is TRH mimetics rovatirelin hydrate synthesis brain disease crystal structure.

We have explored orally effective TSH-releasing hormone (TRH) mimetics showing oral bioavailability and brain penetration by SAR study on the basis of in vivo antagonistic activity on reserpine-induced hypothermia in mice. By primary screening of the synthesized TRH mimetics, we found a novel TRH mimetic: L-pyroglutamyl-[3-(thiazol-4-yl)-L-alanyl]-L-prolinamide with high central nervous system (CNS) effect compared to TRH as a lead compound Further SAR optimization studies of this lead compound led to discovery of a novel orally effective TRH mimetic: 1-{N-[(4S,5S)-(5-methyl-2-oxooxazolidine-4-yl)carbonyl]-3-(thiazol-4-yl)-L-alanyl}-(2R)-2 -methylpyrrolidine trihydrate (Rovatirelin Hydrate), which was selected as a candidate for clin. trials.

ACS Omega published new progress about Bioavailability. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Computed Properties of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Floyd, David M.; Stein, Philip; Wang, Zheng; Liu, Jian; Castro, Steve; Clark, Julie A.; Connelly, Michele; Zhu, Fangyi; Holbrook, Gloria; Matheny, Amy; Sigal, Martina S.; Min, Jaeki; Dhinakaran, Rajkumar; Krishnan, Senthil; Bashyum, Sridevi; Knapp, Spencer; Guy, R. Kiplin published the artcile< Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides>, Synthetic Route of 1003-32-3, the main research area is tetrahydroisoquinolone carboxanilide preparation antimalarial structure activity.

Phenotypic whole-cell screening in erythrocytic co-cultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent anti-malarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3 and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicol. effects, inherent in the more potent primary screening hits such as (I). Analogs (II) and (+)-SJ733 (13i), with structural modifications at each site, were shown to possess excellent anti-malarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogs were identified as the more potent. Based on these studies, the authors have selected (+)-13i for further study as a preclin. candidate.

Journal of Medicinal Chemistry published new progress about Antimalarials. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Synthetic Route of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Ung, Alison T.; Pyne, Stephen G.; Skelton, Brian W.; White, Allan H. published the artcile< Asymmetric synthesis of (1R,2S,3R)-2-acetyl-5-(1,2,3,4-tetrahydroxybutyl)thiazole>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is asym synthesis acetyltetrahydroxybutylthiazole; thiazole acetyltetrahydroxybutyl asym synthesis.

A method for preparing the thiazole analog I of the biol. active compound (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole is reported.

Tetrahedron published new progress about Stereoselective synthesis. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Recommanded Product: Thiazole-5-carboxyaldehyde.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Ulmschneider, Sarah; Mueller-Vieira, Ursula; Klein, Christian D.; Antes, Iris; Lengauer, Thomas; Hartmann, Rolf W. published the artcile< Synthesis and Evaluation of (Pyridylmethylene)tetrahydronaphthalenes/-indanes and Structurally Modified Derivatives: Potent and Selective Inhibitors of Aldosterone Synthase>, Synthetic Route of 1003-32-3, the main research area is heteroarylidene aromatic compound stereoisomer preparation aldosterone oxidase inhibition; pyridylmethylene tetrahydronaphthalene indane stereoisomer preparation aldosterone oxidase inhibition; structure heteroarylidene aromatic compound stereoisomer aldosterone oxidase inhibition; CYP11B2 inhibiting heteroarylidene aromatic compound stereoisomer preparation; selective aldosterone oxidase inhibiting heteroarylidene aromatic compound; mol modeling heteroarylidene aromatic compound binding CYP11B1 CYP11B2.

Heteroarylmethylidene-substituted aromatic compounds such as heteroarylmethyleneindanes I (X = CH, N) are prepared as selective inhibitors of aldosterone synthase (CYP11B2) in the presence of related enzymes such as steroid 11β-hydroxylase (CYP11B1), CYP17, and CYP19. Substituted aromatic ketones, particularly substituted 1-indanones, are reduced with sodium borohydride; substitution of the aromatic alcs. with triphenylphosphine hydrobromide, and Wittig olefination of heterocyclic aldehydes with the generated triphenylphosphonium bromides yields heteroarylmethylene-substituted aromatic compounds such as I (X = CH, N). Both the (E) and the (Z) olefin stereoisomers of many of the heteroarylmethylene-substituted aromatic compounds are prepared Pyridinylmethyleneindane I (X = CH) is the most active inhibitor of CYP11B2 tested, with an IC50 value of 7 nM; pyrimidinylmethyleneindane I (X = N) is the most selective CYP11B2 inhibitor of those tested, with IC50 values of 27 nM for CYP11B2 and 3179 nM for CYP11B1. Mol. modeling of selected compounds and of their complexes with CYP11B1 and CYP11B2 is used to understand the dependence of CYP11B2 inhibition and selectivity on inhibitor structure.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Synthetic Route of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Zhang, Xiaoyu; Luukkonen, Lena M.; Eissler, Christie L.; Crowley, Vincent M.; Yamashita, Yu; Schafroth, Michael A.; Kikuchi, Shota; Weinstein, David S.; Symons, Kent T.; Nordin, Brian E.; Rodriguez, Joe L.; Wucherpfennig, Thomas G.; Bauer, Ludwig G.; Dix, Melissa M.; Stamos, Dean; Kinsella, Todd M.; Simon, Gabriel M.; Baltgalvis, Kristen A.; Cravatt, Benjamin F. published the artcile< DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras>, HPLC of Formula: 1003-32-3, the main research area is DCAF11 targeted protein degradation electrophilic PROTAC cancer.

Ligand-induced protein degradation has emerged as a compelling approach to promote the targeted elimination of proteins from cells by directing these proteins to the ubiquitin-proteasome machinery. So far, only a limited number of E3 ligases have been found to support ligand-induced protein degradation, reflecting a dearth of E3-binding compounds for proteolysis-targeting chimera (PROTAC) design. Here, we describe a functional screening strategy performed with a focused library of candidate electrophilic PROTACs to discover bifunctional compounds that degrade proteins in human cells by covalently engaging E3 ligases. Mechanistic studies revealed that the electrophilic PROTACs act through modifying specific cysteines in DCAF11, a poorly characterized E3 ligase substrate adaptor. We further show that DCAF11-directed electrophilic PROTACs can degrade multiple endogenous proteins, including FBKP12 and the androgen receptor, in human prostate cancer cells. Our findings designate DCAF11 as an E3 ligase capable of supporting ligand-induced protein degradation via electrophilic PROTACs.

Journal of the American Chemical Society published new progress about Androgen receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, HPLC of Formula: 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Xu, Pengfei; Shen, Pei; Wang, Hai; Qin, Lian; Ren, Jie; Sun, Qiushuang; Ge, Raoling; Bian, Jinlei; Zhong, Yi; Li, Zhiyu; Wang, JuBo; Qiu, Zhixia published the artcile< Discovery of imidazopyrrolopyridines derivatives as novel and selective inhibitors of JAK2>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is imidazopyrrolopyridine preparation JAK2 inhibitor SAR mol docking; Imidazopyrrolopyridine; Janus kinase 2 (JAK2); Kinase; Myeloproliferative neoplasms; Selectivity.

Herein,the design, synthesis, and structure-activity relationships of a series of imidazopyrrolopyridines derivatives I [R1 = H, cyclopropyl, 2-chlorophenyl, etc.; R2 = cyanomethyl, 4,4,4-trifluorobutyl, (3-(cyanomethyl)-1-ethylsulfonyl-azetidin-3-yl), etc.] that selectively inhibit Janus kinase 2 (JAK2) was described . These screening cascades revealed that I [R1 = H; R2 = 3-cyanopropyl] was a preferred compound, with IC50 values of 10 nM for JAK2. Moreover, I [R1 = H; R2 = 3-cyanopropyl] was a selective JAK2 inhibitor with 19-fold, >30-fold and >30-fold selectivity over JAK1, JAK3 and TYK2 resp. In cytokine-stimulated cell-based assays, I [R1 = H; R2 = 3-cyanopropyl] exhibited a higher JAK2 selectivity over JAK1 isoforms. Indeed, at a dose of 20 mg/kg compound I [R1 = H; R2 = 3-cyanopropyl], pSTAT3 and pSTAT5 expression was reduced to levels comparable to those of control animals untreated with GM-CSF. Addnl., I [R1 = H; R2 = 3-cyanopropyl] showed a relatively good bioavailability (F = 38%), a suitable half-life time (T1/2 = 1.9 h), a satisfactory metabolic stability, suggesting that I [R1 = H; R2 = 3-cyanopropyl] might be a promising inhibitor of JAK2 for further development research for the treatment of MPNs.

European Journal of Medicinal Chemistry published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Recommanded Product: Thiazole-5-carboxyaldehyde.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Funes-Maldonado, Matias; Sieng, Bora; Amedjkouh, Mohamed published the artcile< Enabling Asymmetric Alkynylation of Azaaryl Aldehydes with Soai Autocatalyst>, Electric Literature of 1003-32-3, the main research area is propargylic alc enantioselective preparation; azaaryl aldehyde dimethylzinc Soai pyrimidylalkanol chiral autocatalyst asym alkynylation.

Synthesis of enantioenriched propargylic alcs. I [R1 = Ph, Si(CH3)3; R2 = 3-pyridyl, thiazol-5-yl, 3-quinolyl, etc.] via enantioselective addition of alkynylzinc reagents to azaaryl aldehydes using Soai (R)-(5-pyrimidyl)alkanol as a chiral catalyst was reported. The autocatalyst can be generated from almost racemic environment to up to 99.5% ee and subsequently propagates this chirality to provide propargylic alcs. in up to 86% ee.

European Journal of Organic Chemistry published new progress about Alcohols, propargyl Role: SPN (Synthetic Preparation), PREP (Preparation). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Electric Literature of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Londregan, Allyn T.; Piotrowski, David W.; Futatsugi, Kentaro; Warmus, Joseph S.; Boehm, Markus; Carpino, Philip A.; Chin, Janice E.; Janssen, Ann M.; Roush, Nicole S.; Buxton, Joanne; Hinchey, Terri published the artcile< Discovery of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as potent agonists of TGR5 via sequential combinatorial libraries>, Synthetic Route of 1003-32-3, the main research area is phenoxydimethylpyrazolecarboxamide combinatorial preparation SAR TGR5 agonist.

Optimization of a high-throughput screening hit led to the discovery of a new series of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as highly potent agonists of TGR5. This novel chemotype was rapidly developed through iterative combinatorial library synthesis. It was determined that in vitro agonist potency correlated with functional activity data from human peripheral blood monocytes.

Bioorganic & Medicinal Chemistry Letters published new progress about Combinatorial library. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Synthetic Route of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica