Month: October 2022

On November 29, 2012, Prime, Michael; Courtney, Stephen Martin; Marston, Richard; Dominguez, Celia; MacDonald, Douglas; Wityak, John published a patent.Application In Synthesis of 1-(Cyclopropanecarbonyl)indoline-5-sulfonyl chloride The title of the patent was Preparation of piperidin-4-yl substituted acrylamides as transglutaminase TG2 inhibitors. And the patent contained the following:

The title compounds I [A = (un)substituted (hetero)aryl, heterocycloalkyl; B = (un)substituted mono- or bicyclic heterocycloalkyl; R1 = H, NO2, COR (wherein R = H, alkyl, cycloalkyl, etc.), etc.; R2 = H or alkyl; R3-R5 = H, F, Cl, alkyl; p = 0-3; q = 0-1], were prepared E.g., a multi-step synthesis of the acrylamide II, starting from tert-Bu piperidin-4-ylcarbamate and 6-chloropyridine-3-sulfonyl chloride, was described. Exemplified compounds I were tested for human TG2 activity. Certain compounds I were found to have IC50 value less than 100 nM (no specific data given). Also provided are pharmaceutical compositions comprising at least one compound or pharmaceutically acceptable salt therein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain disease states responsive to the inhibition of transglutaminase TG2 activity are described. These disease states include neurodegenerative disorders such as Huntington’s disease. Also described are methods of treatment which include administering at least one compound or pharmaceutically acceptable salt thereof as a single active agent or administering at least one compound or pharmaceutically acceptable salt thereof in combination with one or more other therapeutic agents. The experimental process involved the reaction of 1-(Cyclopropanecarbonyl)indoline-5-sulfonyl chloride(cas: 879562-21-7).Application In Synthesis of 1-(Cyclopropanecarbonyl)indoline-5-sulfonyl chloride

The Article related to piperidinyl acrylamide preparation transglutaminase tg2 inhibitor combination chemotherapy, neurodegenerative disorder huntington’s disease treatment piperidinyl acrylamide preparation and other aspects.Application In Synthesis of 1-(Cyclopropanecarbonyl)indoline-5-sulfonyl chloride

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On May 31, 2007, Rios, Ramon; Sunden, Henrik; Vesely, Jan; Zhao, Gui-Ling; Dziedzic, Pawel; Cordova, Armando published an article.Application of 79815-20-6 The title of the article was A simple organocatalytic enantioselective cyclopropanation of α,β-unsaturated aldehydes. And the article contained the following:

A highly chemo- and enantioselective organocatalytic cyclopropanation of α,β-unsaturated aldehydes with bromomalonate and 2-bromoacetoacetate esters is presented. The reaction is catalyzed by chiral amines and gives access to 2-formylcyclopropanes in high yields and up to 99% ee. The experimental process involved the reaction of H-Idc-OH(cas: 79815-20-6).Application of 79815-20-6

The Article related to chiral amine catalyzed enantioselective cyclopropanation alpha beta unsaturated aldehyde, alpha beta unsaturated aldehyde cyclopropanation bromomalonate bromoacetoacetate ester catalyst and other aspects.Application of 79815-20-6

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On March 20, 2019, Kozikowski, Alan P.; Shen, Sida; Pardo, Marta; Tavares, Mauricio T.; Szarics, Dora; Benoy, Veronick; Zimprich, Chad A.; Kutil, Zsofia; Zhang, Guiping; Barinka, Cyril; Robers, Matthew B.; Van Den Bosch, Ludo; Eubanks, James H.; Jope, Richard S. published an article.Application of 52537-00-5 The title of the article was Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and Learning Impairments in a Mouse Model of Fragile X Syndrome. And the article contained the following:

Disease-modifying therapies are needed for Fragile X Syndrome (FXS), as at present there are no effective treatments or cures. Herein, we report on a tetrahydroquinoline-based selective histone deacetylase 6 (HDAC6) inhibitor SW-100, its pharmacol. and ADMET properties, and its ability to improve upon memory performance in a mouse model of FXS, Fmr1-/- mice. This small mol. demonstrates good brain penetrance, low-nanomolar potency for the inhibition of HDAC6 (IC50 = 2.3 nM), with at least a thousand-fold selectivity over all other class I, II, and IV HDAC isoforms. Moreover, through its inhibition of the α-tubulin deacetylase domain of HDAC6 (CD2), in cells SW-100 upregulates α-tubulin acetylation with no effect on histone acetylation and selectively restores the impaired acetylated α-tubulin levels in the hippocampus of Fmr1-/- mice. Lastly, SW-100 ameliorates several memory and learning impairments in Fmr1-/- mice, thus modeling the intellectual deficiencies associated with FXS, and hence providing a strong rationale for pursuing HDAC6-based therapies for the treatment of this rare disease. The experimental process involved the reaction of 6-Chloro-2,3-dihydro-1H-indole(cas: 52537-00-5).Application of 52537-00-5

The Article related to phenylhydroxamate permeability ames neg acetylated memory and learning impairments, ames negative, phenylhydroxamate, acetylated α-tubulin, memory and learning impairments, permeability and other aspects.Application of 52537-00-5

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On September 10, 2010, Kaizawa, Hiroyuki; Sugita, Mari; Azami, Hidenori; Seo, Ryushi; Nomura, Takaho; Yamamoto, Satoshi; Yamamoto, Hirofumi; Tsuchiya, Kazuyuki; Kubota, Hideki; Kamijo, Kazunori published a patent.HPLC of Formula: 52537-00-5 The title of the patent was Preparation of quinoxaline compounds as PDE9 inhibitors. And the patent contained the following:

Title compounds I [one A1 and A2 is N, the other is CR6 or N; one of R1 and R2 is H, halo, (un)substituted alkyl, etc., the other is -CONRaRb; R3 = (un)substituted alkyl, cycloalkyl, cycloalkenyl, etc.; R4, R5 = H or alkyl; R6 = H or alkyl; Ra, Rb = H, (un)substituted alkyl, cycloalkyl, etc.] or salts thereof were prepared For example, reaction of 3-chloro-2-hydrazino-7-methylquinoxaline-6-carboxylic acid Me ester with 3-chloro-4-hydroxybenzaldehyde in the presence of Cu(OAc)2 followed by hydrolysis and EDCI-mediated amidation with 1-pyridin-4-yl-1,2,3,4-tetrahydroisoquinoline afforded compound II. In PDE9 inhibition assays, IC50 of II was 2.3 nM. Compounds I are claimed useful for the treatment of urine collection disorder, urination disorder, etc. The experimental process involved the reaction of 6-Chloro-2,3-dihydro-1H-indole(cas: 52537-00-5).HPLC of Formula: 52537-00-5

The Article related to quinoxaline preparation pde9 inhibitor, urine collection disorder treatment quinoxaline preparation pde9 inhibition, urination disorder treatment quinoxaline preparation pde9 inhibition and other aspects.HPLC of Formula: 52537-00-5

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On May 20, 2010, Shipps, Gerald W., Jr.; Cheng, Cliff C.; Huang, Xiaohua; Achab, Abdelghani Abe; Orth, Peter; Voigt, Johannes H.; Soucy, Kyle Ann published a patent.Reference of 6-Chloro-2,3-dihydro-1H-indole The title of the patent was Preparation of aryldihydrotriazolopyrimidinone derivatives and analogs for use as fatty acid binding protein (FABP) inhibitors. And the patent contained the following:

Title compounds I [G = CR6; X = S, O, NH, etc.; or when X is CR7 or N, then X and G or X and ring Y together form a cycloalkyl or heterocyclyl ring containing 1 to 3 heteroatoms selected from N, O, or S; ring Y = (un)substituted aryl, heteroaryl, heterocyclyl, or cycloalkyl; Z = H, (un)substituted alkyl, cycloalkyl, aryl, etc.; R1 = H, alkyl, haloalkyl, haloalkoxy, etc.; each R2 independently = halo, CN, (un)substituted alkyl, etc.; R6 = absent, H, halo, (un)substituted alkyl, etc.; R7 = H, OH, (un)substituted alkoxy, or alkyl; R9 = H, halo, (un)substituted alkyl, etc.; R10 = H, halo, C(O)OH, C(O)NH2, etc.; m = 1 or 2; n = 0 to 4; with provisions], and their pharmaceutically acceptable salts, are prepared and disclosed as fatty acid binding protein (FABP) inhibitors. Thus, e.g., II was prepared by cyclization of 3-phenyl-1H-1,2,4-triazol-5-amine with Et 4-chloro-3-oxobutanoate followed by esterification with 3-chloro-2-methylphenol. I were evaluated in temperature dependence fluorescence (TdF) assays for FABP4, e.g., II demonstrated an Kd value of >0.001 to 0.5 μM. The experimental process involved the reaction of 6-Chloro-2,3-dihydro-1H-indole(cas: 52537-00-5).Reference of 6-Chloro-2,3-dihydro-1H-indole

The Article related to triazolopyrimidinone aryldihydro derivative preparation fatty acid binding protein inhibitor, aryldihydrotriazolopyrimidinone analog preparation fatty acid binding protein fabp inhibitor and other aspects.Reference of 6-Chloro-2,3-dihydro-1H-indole

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On July 8, 2002, Borbas, Aniko; Szabo, Zoltan B.; Szilagyi, Laszlo; Benyei, Attila; Liptak, Andras published an article.Synthetic Route of 130539-43-4 The title of the article was Dioxane-type (2-naphthyl)methylene acetals of glycosides and their hydrogenolytic transformation into 6-O- and 4-O-(2-naphthyl)methyl (NAP) ethers. And the article contained the following:

α-, β-D-Gluco-, galacto-, 2-deoxy-2-phthalimido-β-D-glucopyranosides with different aglycons (Me, allyl, p-methoxyphenyl, thioethyl) reacted with 2-naphthaldehyde di-Me acetal to give rise to 4,6-O-(2-naphthyl)methylene acetals. The acetals were converted into fully protected compounds bearing benzoyl, benzyl, allyl, p-methoxybenzyl groups. The fully alkylated dioxane-type acetals were hydrogenolyzed with AlH3 (3LiAlH4-AlCl3) reagent to furnish 4-O-NAP/6-OH derivatives All acetals were treated with BH3·Me3N-AlCl3 in THF and a reverse regioselectivity was observed, producing 6-O-NAP/4-OH derivatives Similar regioselectivity was also observed by using NaCNBH3-HCl reagent. In all reactions very mild reaction conditions were required, regioselectivity was better than 93:7, and the isolated yields were between 83-92%. All compounds were characterized by 1H and 13C NMR spectra. Solid-state and solution conformation of Me 2,3-di-O-acetyl-4,6-O-(2-naphthyl)methylene-α-D-galactopyranoside were elucidated by X-ray and NMR measurements. The experimental process involved the reaction of Ethyl 2-deoxy-2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1-thio-beta-D-glucopyranoside(cas: 130539-43-4).Synthetic Route of 130539-43-4

The Article related to naphthyl methylene acetal glycoside preparation, naphthylmethyl ether glycoside regioselective preparation, me acetyl naphthylmethylene galactopyranoside preparation crystal mol structure and other aspects.Synthetic Route of 130539-43-4

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Nonappa; Ahonen, Kari; Lahtinen, Manu; Kolehmainen, Erkki published an article in 2011, the title of the article was Cyclic dipeptides: catalyst/promoter-free, rapid and environmentally benign cyclization of free amino acids.Quality Control of H-Idc-OH And the article contains the following content:

With growing public concern over global warming and the amount of greenhouse gases, it is important to reduce the amount of chems. and eliminate waste, to obtain better results in a simple, selective, safe, and environmentally benign fashion compared to conventional tedious chem. synthesis. Herein, the authors disclose an environmentally benign, rapid, catalyst/promoter/coupling reagent-free cyclization procedure of free amino acids to furnish exclusively cyclic dipeptides (2,5-diketopiperazines, DKPs) in excellent or even quant. yields, along with their solid state self-assembling properties. This process is extremely simple and highly efficient with little or no traditional synthetic skills and without any chromatog. purification Synthesis of structurally diverse DKPs has been achieved with a dramatic decrease in the reaction time, the amount/number of solvents used, a significant increase in the yield and nearly complete elimination of waste. As a result, this is an excellent example for the environmentally benign, clean and green chem. concept. The most exciting outcome of this investigation is an unusual case of chiral self-recognition encountered upon the cyclization of rac-pipecolic acid, which resulted in the formation of the meso-product exclusively. The experimental process involved the reaction of H-Idc-OH(cas: 79815-20-6).Quality Control of H-Idc-OH

The Article related to cyclic dipeptide diketopiperazine preparation amino acid catalyst free cyclization, crystal structure diketopiperazine cyclic dipeptide, pipecolic acid cyclization chiral self recognition and other aspects.Quality Control of H-Idc-OH

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On August 31, 2006, Metzner, L.; Neubert, K.; Brandsch, M. published an article.Reference of H-Idc-OH The title of the article was Substrate specificity of the amino acid transporter PAT1. And the article contained the following:

The proton coupled amino acid transporter PAT1 expressed in intestine, brain, and other organs accepts L- and D-proline, glycine, and L-alanine but also pharmaceutically active amino acid derivatives such as 3-amino-1-propanesulfonic acid, L-azetidine-2-carboxylic acid, and cis-4-hydroxy-D-proline as substrates. We systematically analyzed the structural requirements for PAT1 substrates by testing 87 amino acids, proline homologs, indoles, and derivatives Affinity data and effects on membrane potential were determined using Caco-2 cells. For aliphatic amino acids, a blocked carboxyl group, the distance between amino and carboxyl group, and the position of the hydroxyl group are affinity limiting factors. Methylation of the amino group enhances substrate affinity. Hetero atoms in the proline template are well tolerated. Aromatic α-amino acids display low affinity. PAT1 interacts strongly with heterocyclic aromatic acids containing an indole scaffold. The structural requirements of PAT1 substrates elucidated in this study will be useful for the development of prodrugs. The experimental process involved the reaction of H-Idc-OH(cas: 79815-20-6).Reference of H-Idc-OH

The Article related to amino acid transport pat1 transporter intestine epithelium, carboxyl hydroxyl amino imino group amino acid structure transport, prodrug drug transport metabolism amino group methylation pat1 and other aspects.Reference of H-Idc-OH

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On December 2, 1999, Mavunkel, Babu J.; Liu, David Y.; Schreiner, George F.; Lewicki, John A.; Perumattam, John J. published a patent.Reference of 6-Chloro-1H-indole-5-carboxylic acid The title of the patent was Heterocyclic compounds and methods to treat cardiac failure and other disorders. And the patent contained the following:

Compounds I and II [Z1, Z2 = CR4, N; R4 = H, alkyl, aryl, each of said alkyl or aryl optionally including one or more heteroatoms selected from O, S and N and optionally substituted by one or more of halo, OR, SR, NR2, RCO, CO2R, CONR2, O2CR, NROCR and R = H, alkyl, CN, oxo, etc.; R1 = Q and X1 = CO or an isostere; m = 0, 1; Y = alkyl, aryl, arylalkyl; YY = alkylene bridge; n = 0, 2; Z3 = CH, N; X2 = CH, CH2 or an isostere; Ar = one or two Ph moieties directly coupled to X2 optionally substituted by halo, nitro, alkyl, etc.; R2 = H, alkyl, aryl; R3 = H, halo, NO2, alkyl, alkenyl, etc.], selective inhibitors of p38α kinase, were prepared E.g., 4-benzylpiperidinylindole-5-carboxamide was prepared The experimental process involved the reaction of 6-Chloro-1H-indole-5-carboxylic acid(cas: 256935-86-1).Reference of 6-Chloro-1H-indole-5-carboxylic acid

The Article related to heterocyclic compound preparation p38 kinase inhibitor, benzimidazole preparation p38 kinase inhibitor, benzotriazole preparation p38 kinase inhibitor, indole preparation p38 kinase inhibitor and other aspects.Reference of 6-Chloro-1H-indole-5-carboxylic acid

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On March 30, 2006, Kerns, Jeffrey K.; Lindenmuth, Michael; Lin, Xichen; Nie, Hong; Thomas, Sonia M. published a patent.Electric Literature of 860624-88-0 The title of the patent was Indole derivatives as IKK2 inhibitors and their preparations, pharmaceutical compositions, and use for treatment of diseases associated with inappropriate IKK2 activity such as rheumatoid arthritis, asthma and chronic obstructive pulmonary disease. And the patent contained the following:

The invention is directed to indole carboxamide derivatives of formula I. Compounds of formula I wherein R1 is H, halo or YZ; R2 and R3 are independently H, F or Cl; Y is a bond, C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene; Z is (un)substituted (hetero)aryl; U is a bond, C1-6 alkylene or C2-6 alkenylene; V is (un)substituted Ph, (un)substituted 5- or 6-membered heteroaryl, (un)substituted 5- to 7-membered heterocycloalkyl, (un)substituted C5-7 cycloalkyl or (un)substituted C5-7 cycloalkenyl; and their pharmaceutically acceptable salts, solvates, or polymorphs thereof are claimed in this invention. The compounds of the invention are inhibitors of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKKss) activity, such as rheumatoid arthritis, asthma, and COPD (chronic obstructive pulmonary disease). Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting IKK2 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. Example compound II was prepared by N-Boc protection of indoline followed by acylation with Me chloroformate to give Me 1-(tert-butoxycarbonyl)indoline-7-carboxylate, which underwent bromination to give 5-bromo derivative, which was deprotected; the resulting Me 5-bromoindoline-7-carboxylate was dehydrated to give the Me 5-bromoindolecarboxylate, which upon hydrolysis gave the 5-bromo-7-indolecarboxylic acid, which underwent cross-coupling with phenylboronic acid; the resulting 5-phenylindole-7-carboxylic acid was converted to the corresponding indolecarboxamide, which underwent condensation with N-benzyl-4-piperidinone to give 3-(4-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-5-phenylindole-7-carboxamide, which was subjected to hydrogenation; the resulting 3-(4-piperidinyl)-5-phenylindole-7-carboxamide was sulfonylated with 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethanesulfonyl chloride to give 3-[1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethanesulfonyl]piperidin-4-yl]-5-methyl-1H-indole-7-carboxamide, which was reacted with to give compound II. Addnl. 315 example compounds were prepared by similar methods. All the invention compounds were evaluated for their IKK2 kinase inhibitory activity. From the IKK2 assay, it was determined that example compound II along with several other compounds have pIC50 values of 5.0 or greater. In the monocyte assay, most of the tested compound showed IC50 values or less than 10μM. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).Electric Literature of 860624-88-0

The Article related to indole preparation pharmaceutical composition ikk2 inhibitor, ikk2 inhibitor treatment rheumatoid arthritis asthma copd indole preparation, treatment disease associated ikk2 indole preparation and other aspects.Electric Literature of 860624-88-0

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles