- Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids via Hydrogen Atom Transfer
-
The oxidation of primary alcohols and aldehydes to the corresponding carboxylic acids is a fundamental reaction in organic synthesis. In this paper, we report a new chemoselective process for the oxidation of primary alcohols and aldehydes. This metal-free reaction features a new oxidant, an easy to handle procedure, high isolated yields, and good to excellent functional group tolerance even in the presence of vulnerable secondary alcohols and tert-butanesulfinamides.
- Tan, Wen-Yun,Lu, Yi,Zhao, Jing-Feng,Chen, Wen,Zhang, Hongbin
-
supporting information
p. 6648 - 6653
(2021/09/08)
-
- JANUS KINASE (JAK) FAMILY INHIBITOR, PREPARATION OF SAME, AND APPLICATIONS THEREOF
-
A 7-azaindole derivative having the structure of formula (I), a pharmaceutical composition containing the compound of formula (I), and uses of the compound in preparing a medicament for preventing or treating Janus kinase (JAK) family-related diseases, specifically, uses in preventing or treating inflammatory diseases related to protein tyrosine kinase.
- -
-
Paragraph 0083-0085
(2021/12/18)
-
- Optimization of Small Molecules That Sensitize HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity
-
With approximately 37 million people living with HIV worldwide and an estimated 2 million new infections reported each year, the need to derive novel strategies aimed at eradicating HIV-1 infection remains a critical worldwide challenge. One potential strategy would involve eliminating infected cells via antibody-dependent cellular cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to conceal epitopes located in its envelope glycoprotein (Env) that are recognized by ADCC-mediating antibodies present in sera from HIV-1 infected individuals. Our aim is to circumvent this evasion via the development of small molecules that expose relevant anti-Env epitopes and sensitize HIV-1 infected cells to ADCC. Rapid elaboration of an initial screening hit using parallel synthesis and structure-based optimization has led to the development of potent small molecules that elicit this humoral response. Efforts to increase the ADCC activity of this class of small molecules with the aim of increasing their therapeutic potential was based on our recent cocrystal structures with gp120 core.
- Abrams, Cameron F.,Chapleau, Jean-Philippe,Ding, Shilei,Grenier, Melissa C.,Pazgier, Marzena,Sherburn, Rebekah,Smith, Amos B.,Somisetti, Sambasivarao,Tolbert, William D.,Finzi, Andrés,Sch?n, Arne,Vézina, Dani
-
supporting information
p. 371 - 378
(2019/12/02)
-
- SMALL MOLECULES THAT SENSITIZE HIV-1 INFECTED CELLS TO ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY
-
Compounds and methods of treating HIV-1 in a human infected with HIV-1 or preventing HIV-1 infection in a human susceptible to infection with HIV-1 are provided. The compounds are of formula (I), (II), and (IA), wherein R1-R7, X, X', Y, Y', Z, and n are defined herein, and the methods comprises administering therapeutically effective amounts of these compounds to the human.
- -
-
Paragraph 00106
(2020/02/23)
-
- Compounds used as JAK inhibitor, and use of compounds
-
The invention provides compounds used as a JAK inhibitor, and a use of the compounds, and concretely provides compounds (represented by formula (I)) with JAK inhibition activity or a stereoisomer, a geometric isomer, a tautomer, a racemate, a nitrogen oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and a medicinal composition including the compounds. The invention also discloses a use of the compounds or the medicinal composition thereof in the preparation of medicines used for treating autoimmune diseases or proliferative diseases.
- -
-
Paragraph 0453; 0454; 0455
(2017/08/27)
-
- Preparation method of 1-BOC-3-hydroxymethyl pyrrolidine
-
The invention discloses a preparation method of 1-Boc-3-hydroxymethyl pyrrolidine. The preparation method uses epichlorohydrin as a raw material, 3-hydroxymethyl pyrrolidine is obtained through reduction and cyclization reaction, then the 1-Boc-3-hydroxymethyl pyrrolidine is prepared through Boc protection reaction, then 1-BOC-3-methyl formate pyrrolidine is prepared through carboxylation reaction and esterification reaction, and finally the 1-BOC-3-methyl formate pyrrolidine and lithium aluminum hydride are catalyzed by a catalyst to prepare the 1-BOC-3-hydroxymethyl pyrrolidine. The preparation method is high in product synthesis rate, high in product purity and low in production cost, and the raw materials are cheap and easy to obtain.
- -
-
Paragraph 0021; 0026
(2017/05/10)
-
- N-(1-HYDROXY-3-(PYRROLIDINYL)PROPAN-2-YL)PYRROLIDINE-3-CARBOXAMIDE DERIVATIVES AS GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
-
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and compounds I for use to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).
- -
-
Paragraph 000491
(2015/05/19)
-
- Highly selective asymmetric Rh-catalyzed hydroformylation of heterocyclic olefins
-
A small family of new chiral hybrid, diphosphorus ligands, consisting of phosphine-phosphoramidites L1 and L2 and phosphine-phosphonites L3a-c, was synthesized for the application in Rh-catalyzed asymmetric hydroformylation of heterocyclic olefins. High-pressure (HP)-NMR and HP-IR spectroscopy under 5-10 bar of syngas has been employed to characterize the corresponding catalyst resting state with each ligand. Indole-based ligands L1 and L2 led to selective ea coordination, while the xanthene derived system L3c gave predominant ee coordination. Application of the small bite-angle ligands L1 and L2 in the highly selective asymmetric hydroformylation (AHF) of the challenging substrate 2,3-dihydrofuran (1) yielded the 2-carbaldehyde (3) as the major regioisomer in up to 68% yield (with ligand L2) along with good ees of up to 62%. This is the first example in which the asymmetric hydroformylation of 1 is both regio- and enantioselective for isomer 3. Interestingly, use of ligand L3c in the same reaction completely changed the regioselectivity to 3-carbaldehyde (4) with a remarkably high enantioselectivity of 91%. Ligand L3c also performs very well in the Rh-catalyzed asymmetric hydroformylation of other heterocyclic olefins. Highly enantioselective conversion of the notoriously difficult substrate 2,5-dihydrofuran (2) is achieved using the same catalyst, with up to 91% ee, concomitant with complete regioselectivity to the 3-carbaldehyde product (4) under mild reaction conditions. Interestingly, the Rh-catalyst derived from L3c is thus able to produce both enantiomers of 3-carbaldehyde 4, simply by changing the substrate from 1 to 2. Furthermore, 85% ee was obtained in the hydroformylation of N-acetyl-3-pyrroline (5) with exceptionally high regioselectivities for 3-carbaldehyde 8Ac (>99%). Similarly, an ee of 86% for derivative 8Boc was accomplished using the same catalyst system in the AHF of N-(tert-butoxycarbonyl)-3-pyrroline (6). These results represent the highest ees reported to date in the AHF of dihydrofurans (1, 2) and 3-pyrrolines (5, 6).
- Chikkali, Samir H.,Bellini, Rosalba,De Bruin, Bas,Van Der Vlugt, Jarl Ivar,Reek, Joost N. H.
-
p. 6607 - 6616
(2012/06/15)
-
- Enzymatic resolution of n-substituted-β-prolines
-
A general and straightforward strategy for enzymatic resolution of N-substituted-β-proline has been successfully designed and developed in our research laboratories. A first affinity screen is followed by ratio enzyme/substrate optimization to source our
- Mendiola, Javier,Garcia-Cerrada, Susana,De Frutos, Oscar,De La Puente, Maria Luz,Gu, Rui Lin,Khau, Vien V.
-
scheme or table
p. 292 - 296
(2010/04/22)
-
- Synthesis of functionalized nitrogen heterocycles by radical decarboxylation of β- and γ-amino acids
-
Iodinated or oxygenated nitrogen heterocycles are obtained by radical decarboxylation of β- and γ-amino acids. This mild, versatile reaction is applied to the synthesis of bioactive products, such as 4-arylpiperidines, hydroxylated piperidines, and new antifungal agents.
- Boto, Alicia,Hernandez, Rosendo,De Leon, Yolanda,Murguia, Jose R.,Rodriguez-Afonso, Abigail
-
p. 673 - 682
(2007/10/03)
-
- Novel phosphorus radical-based routes to horsfiline
-
(Chemical Equation Presented) Radicals derived from the phosphorus reagents, ethylpiperidine hypophosphite (EPHP) and diethylphosphine oxide (DEPO), are used in two related approaches to synthesis of the alkaloid horsfiline (1). In particular, DEPO proves
- Murphy, John A.,Tripoli, Regis,Khan, Tanweer A.,Mali, Umesh W.
-
p. 3287 - 3289
(2007/10/03)
-
- Cathepsin cysteine protease inhibitors
-
This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of Cathepsins K and L. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
- -
-
-
- Novel, nonpeptidic cyanamides as potent and reversible inhibitors of human cathepsins K and L
-
Compounds containing a 1-cyanopyrrolidinyl ring were identified as potent and reversible inhibitors of cathepsins K and L. The original lead compound 1 inhibits cathepsins K and L with IC50 values of 0.37 and 0.45 μM, respectively. Modification of compound 1 by replacement of the quinoline moiety led to the synthesis of N-(1-cyano-3-pyrrolidinyl)benzenesulfonamide (2). Compound 2 was found to be a potent inhibitor of cathepsins K and L with a Ki value of 50 nM for cathepsin K. Replacement of the 1-cyanopyrrolidine of compound 2 by a 1-cyanoazetidine increased the potency of the inhibitor by 10-fold. This increase in potency is probably due to an enhanced chemical reactivity of the compound toward the thiolate of the active site of the enzyme. This is demonstrated when the assay is performed in the presence of glutathione at pH 7.0 which favors the formation of a GSH thiolate anion. Under these assay conditions, there is a loss of potency in the 1-cyanoazetidine series due to the formation of an inactive complex between the GSH thiolate and the 1-cyanoazetidine inhibitors. 1-Cyanopyrrolidinyl inhibitors exhibited time-dependent inhibition which allowed us to determine the association and dissociation rate constants with human cathepsin K. The kinetic data obtained showed that the increase of potency observed between different 1-cyanopyrrolidinyl inhibitors is due to an increase of kon values and that the association of the compound with the enzyme fits an apparent one-step mechanism. 13C NMR experiments performed with the enzyme papain showed that compound 2 forms a covalent isothiourea ester adduct with the enzyme. As predicted by the kinetic analysis, the addition of the irreversible inhibitor E64 to the enzyme-cyanopyrrolidinyl complex totally abolished the signal of the isothiourea bond as observed by 13C NMR, thereby demonstrating that the formation of the covalent bond with the active site cysteine residue is reversible. Finally, compound 2 inhibits bone resorption in an in vitro assay involving rabbit osteoclasts and bovine bone with an IC50 value of 0.7 μM. 1-Cyanopyrrolidine represents a new class of nonpeptidic compounds that inhibit cathepsin K and L activity and proteolysis of bone collagen.
- Falgueyret,Oballa,Okamoto,Wesolowski,Aubin,Rydzewski,Prasit,Riendeau,Rodan,Percival
-
-
- Synthesis and muscarinic activities of 1,2,4-thiadiazoles
-
A series of novel 1,2,4-thiadiazoles bearing a mono- or bicyclic amine at C5 were prepared. Quinuclidine and 1-azabicyclo[2.2.1]heptane derivatives were synthesized by reaction of the lithium enolate of the 3-methoxycarbonyl compounds followed by ester hy
- MacLeod,Baker,Freedman,Patel,Merchant,Roe,Saunders
-
p. 2052 - 2059
(2007/10/02)
-
- Pyrrolidine derivatives
-
Pyrrolidine derivatives which have the formula SPC1 Wherein R and R1 each is hydrogen, --(CH2)6 COOH, --(CH2)6 COO-- lower alkyl, or --(CH2)6 COO benzyl and R2 is hydrogen, --CO--O--(CH2)5 CH3, --CO--NH--(CH2)5 CH3 --(CH2)7 CH3 or --CH=CH--CH(OH)--(CH2)4 --CH3, at least one of R and R1 is hydrogen and R1 and R2 are not both hydrogen, are new compounds which are useful as inhibitors of prostaglandin dehydrogenase and as potentiators of prostaglandin activity.
- -
-
-