Tag: M.W=100-150

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>, Electric Literature of 1003-32-3, 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 Chemistrypublished new progress about Antitumor agents. 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

Mallo-Abreu, Ana; Prieto-Diaz, Ruben; Jespers, Willem; Azuaje, Jhonny; Majellaro, Maria; Velando, Carmen; Garcia-Mera, Xerardo; Caamano, Olga; Brea, Jose; Loza, Maria I.; Gutierrez-de-Teran, Hugo; Sotelo, Eddy published the artcile< A Nitrogen-Walk Approach to Explore Bioisosteric Replacements in a Series of Potent A2B Adenosine Receptor Antagonists>, HPLC of Formula: 1003-32-3, the main research area is dihydrobenzoimidazopyrimidine carboxylate preparation SAR docking A2B adenosine receptor antagonist.

A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists was carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates I [R = H, cyclopentyl, Ph, etc.; R1 = Et, i-Pr], which contain 18 different pentagonal heterocyclic frameworks at position 4, was synthesized and evaluated. This study enabled the identication of new ligands that combine remarkable affinity (Ki < 30 nM) and exquisite selectivity. The SAR trends identified were substantiated by a mol. modeling study, based on a receptor-driven docking model and including a systematic free energy perturbation (FEP) study. Preliminary evaluation of the CYP3A4 and CYP2D6 inhibitory activity in optimized ligands evidenced weak and negligible activity resp. The stereospecific interaction between hA2BAR and the eutomer of the most attractive novel antagonist (S)-II (Ki = 3.66 nM) was validated. Journal of Medicinal Chemistrypublished new progress about Adenosine A2B 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

Lam, P. Y. S.; Deudon, S.; Hauptman, E.; Clark, C. G. published the artcile< α-Nitrogen-activating effect in the room temperature copper-promoted N-arylation of heteroaryl carboxamides with phenylsiloxane or 4-tolylboronic acid>, Application In Synthesis of 31825-95-3, the main research area is nitrogen heteroaromatic carboxamide phenylsiloxane arylation; tolylboronate nitrogen heteroaromatic carboxamide arylation; cross coupling nitrogen heteroaromatic carboxamide phenylsiloxane.

α-N-containing heteroaryl carboxamides undergo Cu-promoted N-phenylation with hypervalent PhSi(OMe)3 at room temperature, in the absence of base and in air. Arylboronic acid can substitute for PhSi(OMe)3 as the organometalloid. The α-heteroatom chelating effect is in the decreasing order of N > O, S. This discovery opens up the possibility of using other α-N functional groups to direct the N-arylation of peptides and simple amides under conditions as mild as that of amide bond formation.

Tetrahedron Letterspublished new progress about Amides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (heteroaromatic). 31825-95-3 belongs to class thiazole, and the molecular formula is C5H6N2OS, Application In Synthesis of 31825-95-3.

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

Pan, Qingqing; Deng, Xin; Gao, Wenxia; Chang, Jing; Pu, Yuji; He, Bin published the artcile< ROS triggered cleavage of thioketal moiety to dissociate prodrug nanoparticles for chemotherapy>, Application In Synthesis of 96-53-7, the main research area is cancer doxorubicin PEG nanoparticle delivery ROS; Cancer therapy; Dissociation; Prodrug nanoparticle; ROS-responsive; Thioketal.

With the utilization of high concentration reactive oxygen species (ROS) in tumor microenvironment, PEG-doxorubicin (PEG-DOX) prodrug was synthesized via a thioketal moiety as the linker, which was ROS cleavable to trigger DOX release from the self-assembled prodrug nanoparticles. The in vitro ROS sensitivity of prodrug nanoparticles (NPs) was investigated in Fenton agent and H2O2, and the disassembly of NPs was more sensitive to Fenton reagent. After internalized in HepG2 cells via endocytosis, the cellular ROS consuming test revealed intracellular DOX release. The pharmacokinetics and biodistribution study demonstrated that the in vivo elimination of NPs was significantly improved and the NPs were passively targeted to tumor tissues via EPR effect. The ROS-responsive prodrug NPs exhibited excellent antitumor activity in HepG2 tumor-bearing nude mice, remarkably induced tumor cells apoptosis and reduced the systemic toxicity of DOX. Our study revealed the ROS responsive prodrug nanoparticle is an effective strategy to fabricate nanomedicine for cancer chemotherapy.

Colloids and Surfaces, B: Biointerfacespublished new progress about Aggregation. 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, Application In Synthesis of 96-53-7.

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

Jaffett, Victor A.; Nerurkar, Alok; Cao, Xufeng; Guzei, Ilia A.; Golden, Jennifer E. published the artcile< Telescoped synthesis of C3-functionalized (E)-arylamidines using Ugi-Mumm and regiospecific quinazolinone rearrangements>, Safety of Thiazole-5-carboxyaldehyde, the main research area is arylamidine stereoselective preparation; azidobenzoic acid isocyanide aldehyde bismethylaminoethane Ugi Mumm regiospecific rearrangement.

An efficient four-step, six-transformation protocol was developed to afford bioactive N-alkyl- or N-arylamide (E)-arylamidines I (R1 = Cy, 4-OMeC6H4, i-Pr, etc.; R2 = i-Pr, i-Bu, H, etc.; R3 = H, 5-CH3, 5-F, etc.) featuring strategic amidine C3 modifications which were inaccessible or low yielding by previous methods. This synthetic approach, exemplified with 24 amidines and requiring only a single purification, highlights a multicomponent Ugi-Mumm rearrangement to afford highly diversified quinazolinones which undergo regiospecific rearrangement to afford new amidines. The method extensively broadens the structural scope of this new class of trisubstituted amidines and demonstrates the tolerance of regional C3 amidine steric bulk, visualized with X-ray crystallog. anal.

Organic & Biomolecular Chemistrypublished new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Safety of Thiazole-5-carboxyaldehyde.

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

Wang, Mu-Xuan; Qin, Hong-Wei; Liu, Chao; Lv, Shen-Ming; Chen, Jia-Shu; Wang, Chun-Gu; Chen, Ying-Ying; Wang, Jia-Wei; Sun, Jin-Yue; Liao, Zhi-Xin published the artcile< Synthesis and biological evaluation of thiazolidine-2-thione derivatives as novel xanthine oxidase inhibitors>, SDS of cas: 96-53-7, the main research area is thiazolidine thione preparation xanthine oxidase inhibitor SAR mol modeling.

In this study, a series of novel thiazolidine-2-thione derivatives I (R1 = Et, Pr, Ph, benzyl) and II (R2 = Et, 3-pyridyl, cyclohexyl, etc.) were synthesized as XO inhibitors, and the XO inhibitory potencies of obtained compounds I and II was evaluated by in vitro enzyme catalysis. The result shown that compound II [R2 = (4-fluorobenzene)sulfonyl] behaved the strongest XO inhibitory activity with an IC50 value of 3.56μmol/L, which was approx. 2.5-fold more potent than allopurinol. The structure-activity relationship revealed that the phenyl-sulfonamide group was indispensable for thiazolidine-2-thione derivatives II [R2 = (4-fluorobenzene)sulfonyl] to produce XO inhibitory activity. The enzyme inhibition kinetics analyses confirmed that compound II [R2 = (4-fluorobenzene)sulfonyl] exerted a mixed-type XO inhibition. Addnl., the mol. docking results suggested that the 4-fluorophenyl-sulfonyl moiety could interact with Gly260 and Ile264 in the innermost part of the active pocket through 2 hydrogen bonds, while the thiazolidinethione moiety could form two hydrogen bonds with Glu263 and Ser347 in hydrophobic pockets. In summary, the results described above suggested that compound II [R2 = (4-fluorobenzene)sulfonyl] could be a valuable lead compound for the treatment of hyperuricemia as a novel XO inhibitor.

PLoS Onepublished new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, SDS of cas: 96-53-7.

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

da Silva, Monize M.; Ribeiro, Gabriel H.; de Camargo, Mariana S.; Ferreira, Antonio G.; Ribeiro, Leandro; Barbosa, Marilia I. F.; Deflon, Victor M.; Castelli, Silvia; Desideri, Alessandro; Correa, Rodrigo S.; Ribeiro, Arthur B.; Nicolella, Heloiza D.; Ozelin, Saulo D.; Tavares, Denise C.; Batista, Alzir A. published the artcile< Ruthenium(II) Diphosphine Complexes with Mercapto Ligands That Inhibit Topoisomerase IB and Suppress Tumor Growth In Vivo>, Application In Synthesis of 96-53-7, the main research area is melanoma antitumor lung breast cancer hTopIB docking ruthenium complexes.

Ruthenium(II) complexes (Ru1-Ru5), with the general formula [Ru(N-S)(dppe)2]PF6, bearing two 1,2-bis(diphenylphosphino)ethane (dppe) ligands and a series of mercapto ligands (N-S), have been developed. The combination of these ligands in the complexes endowed hydrophobic species with high cytotoxic activity against five cancer cell lines. For the A549 (lung) and MDA-MB-231 (breast) cancer cell lines, the IC50 values of the complexes were 288- to 14-fold lower when compared to cisplatin. Furthermore, the complexes were selective for the A549 and MDA-MB-231 cancer cell lines compared to the MRC-5 nontumor cell line. The multitarget character of the complexes was investigated by using calf thymus DNA (CT DNA), human serum albumin, and human topoisomerase IB (hTopIB). The complexes potently inhibited hTopIB. In particular, complex [Ru(dmp)(dppe)2]PF6 (Ru3) (I), bearing the 4,6-diamino-2-mercaptopyrimidine (dmp) ligand, effectively inhibited hTopIB by acting on both the cleavage and religation steps of the catalytic cycle of this enzyme. Mol. docking showed that the Ru1-Ru5 complexes have binding affinity by active sites on the hTopI and hTopI-DNA, mainly via π-alkyl and alkyl hydrophobic interactions, as well as through hydrogen bonds. Complex Ru3 displayed significant antitumor activity against murine melanoma in mouse xenograph models, but this complex did not damage DNA, as revealed by Ames and micronucleus tests.

Inorganic Chemistrypublished new progress about Antitumor agents. 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, Application In Synthesis of 96-53-7.

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

Yin, Liuyan; Wang, Lanzhi published the artcile< Chemo-/regio-selective synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines using Lewis acid, CeCl3·7H2O>, Application of C4H3NOS, the main research area is dihydrobenzodiazepine aryl acetyl preparation chemoselective regioselective; phenylenediamine aryl aldehyde butynone condensation Lewis acid catalyst.

A unique and efficient method has been developed for the one-pot synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines I (Ar = 2-thiazolyl, 2-thienyl, 4-ClC6H4, etc.) in good yields using o-phenylenediamine, aromatic aldehyde and 3-butyn-2-one in the presence of a catalytic amount of CeCl3·7H2O in ethanol at ambient temperature An exclusive chemo-/regio-selective formation of substituted isomers of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines II (Ar = 2-thiazolyl, 2-thienyl, 4-ClC6H4, etc.; R = CH3, F, Cl, Br) was achieved from the different reaction process, by exploiting the strategy based on the variation of electrophilicity of the two electrophilic centers of aromatic aldehyde, 3-butyn-2-one and nucleophilic profiles of substituted o-phenylenediamines. This process offers an easy and efficient synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines in high yields.

Tetrahedron Letterspublished new progress about Aryl aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Application of C4H3NOS.

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

Isbrandt, Eric S.; Nasim, Amrah; Zhao, Karen; Newman, Stephen G. published the artcile< Catalytic Aldehyde and Alcohol Arylation Reactions Facilitated by a 1,5-Diaza-3,7-diphosphacyclooctane Ligand>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is aryl iodide aldehyde nickel diazadiphosphacyclooctane catalyst reductive Heck arylation; primary alc aryliodide nickel diazadiphosphacyclooctane catalyst reductive Heck arylation; secondary alc preparation.

A catalytic method to access secondary alcs. by the coupling of aryl iodides was reported. Either aldehydes or alcs. can be used as reaction partners, making the transformation reductive or redox-neutral, resp. The reaction was mediated by a Ni catalyst and a 1,5-diaza-3,7-diphosphacyclooctane. This P2N2 ligand, which was previously been unrecognized in cross-coupling and related reactions, was found to avoid deleterious aryl halide reduction pathways that dominate with more traditional phosphines and NHCs. An interrupted carbonyl-Heck type mechanism was proposed to be operative, with a key 1,2-insertion step forging the new C-C bond and forming a nickel alkoxide that may be turned over by an alc. reductant. The same catalyst was also found to enable synthesis of ketone products from either aldehydes or alcs., demonstrating control over the oxidation state of both the starting materials and products.

Journal of the American Chemical Societypublished new progress about Aldehydes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 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

Tao, Zhi-Fu; Chen, Zehan; Bui, Mai-Ha; Kovar, Peter; Johnson, Eric; Bouska, Jennifer; Zhang, Haiying; Rosenberg, Saul; Sowin, Thomas; Lin, Nan-Horng published the artcile< Macrocyclic ureas as potent and selective Chk1 inhibitors: An improved synthesis, kinome profiling, structure-activity relationships, and preliminary pharmacokinetics>, HPLC of Formula: 1003-32-3, the main research area is macrocyclic urea preparation selective Chk1 inhibitor; structure macrocyclic urea selectivity Chk1 inhibitor pharmacokinetics; doxorubicin macrocyclic urea combination antitumor activity; kinase selectivity inhibition macrocyclic urea; amine protection key step preparation macrocyclic urea; trimethylsilylethoxycarbonyl group protection amine key step preparation macrocyclic urea.

Macrocyclic ureas such as I [R = H, H2N, MeNH, Me2N, (HOCH2CH2)2N, HOCH2CH2NH, 5-thiazolylmethylamino, 4-pyridinecarbonylamino, 2-chloro-4-pyridinecarbonylamino, (S)-MeCH(NH2)CONH, 2-(4-morpholinyl)ethoxycarbonylamino, 2-oxo-3-oxazolidinyl, HO, HOCH2CH2O, HO(CH2)3O, MeO(CH2)3, 2-(4-morpholinyl)ethoxy, 3-(4-morpholinyl)propoxy, 4-(1-piperidinyl)-1-piperidinecarbonyloxy, (HO)2P(:O); X = CH2CH2, CH:CH] are prepared as selective Chk1 kinase inhibitors and as agents for the sensitization of tumor cells to doxorubicin for potential use as anticancer agents. The structure-activity relationship for Chk1 inhibition of substituted 14-membered urea macrocycles is determined, leading to the identification of sixteen compounds which are effective inhibitors of Chk1. The active urea macrocycles significantly sensitize tumor cells to the DNA-damaging antitumor agent doxorubicin in a cell-based assay and efficiently abrogate the doxorubicin-induced G2/M and camptothecin-induced S checkpoints. The inhibition of a panel of 120 kinases by I (R = 5-thiazolemethylamino; X = CH2CH2; II) is determined; II inhibits Chk1 at 100-fold lower concentrations than any of the other kinases in the panel. Pharmacokinetic studies of I (R = H; X = CH2CH2, CH2CH2CH2) suggest that 14-membered macrocycles such as I (R = H; X = CH2CH2) may possess better pharmacokinetic properties than their 15-membered counterparts such as I (R = H; X = CH2CH2CH2). An improved method for the preparation of amine-containing urea macrocycles I [R = H2N; X = CH:CH, CH2CH2] is determined; protection of the free amino group of a bisallyl diaryl urea intermediate with the trimethylsilylethoxycarbonyl group allows ring-closing macrocyclocondensation in the presence of the Hoveyda-Grubbs catalyst without the formation of inseparable and highly colored byproducts.

Bioorganic & Medicinal Chemistry Letterspublished new progress about Antitumor agents. 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