- Synthetic process of anti-hyperglycemic drug intermediate R-3-amino-piperidine dihydrochloride
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The invention relates to a synthetic process of an anti-hyperglycemic drug intermediate R-3-amino-piperidine dihydrochloride. The synthetic process comprises the steps: using inexpensive L-glutamic acid as a starting material, and performing esterification, amino protection, reduction, hydroxyl protection, substitution, cyclization and removal of protecting groups for amino groups so as to obtainthe R-3-amino-piperidine dihydrochloride. Compared with the prior art, the synthetic process has cheap and easily available raw materials, good selectivity, good atomic economy, high total yield and mild reaction conditions, and is suitable for industrial production.
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Paragraph 0056-0059
(2019/11/12)
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- Synthetic Indolactam V Analogues as Inhibitors of PAR2-Induced Calcium Mobilization in Triple-Negative Breast Cancer Cells
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Human proteinase-activated receptor 2 (PAR2), a transmembrane G-protein-coupled receptor (GPCR), is an attractive target for a novel anticancer therapy, as it plays a critical role in cell migration and invasion. Selective PAR2 inhibitors therefore have potential as anti-metastatic drugs. Knowing that the natural product teleocidin A2 is able to inhibit PAR2 in tumor cells, the goal of the present study was to elaborate structure–activity relationships and to identify potent PAR2 inhibitors with lower activity against the adverse target, protein kinase C (PKC). For this purpose, an efficient gram-scale total synthesis of indolactam V (i.e., the parent structure of all teleocidins) was developed, and a library of derivatives was prepared. Some compounds were indeed found to exhibit high potency as PAR2 inhibitors at low nanomolar concentrations with improved selectivity (relative to teleocidin A2). The pseudopeptidic fragment bridging the C3 and C4 positions of the indole core proved to be essential for target binding, whereas activity and target selectivity depends on the substituents at N1 or C7. This study revealed novel derivatives that show high efficacy in PAR2 antagonism combined with increased selectivity.
- Stein, Jan,Stahn, Sonja,Neud?rfl, J?rg-M.,Sperlich, Julia,Schmalz, Hans-Günther,Teusch, Nicole
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supporting information
p. 147 - 154
(2018/02/06)
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- CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF
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The present technology relates to compounds, kits, compositions, and methods useful for the treatment of fibrotic disease. In some aspects, the present technology provides for treatment of various diseases or disorders associated or mediated, at least in part, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is generally applicable to compounds which inhibit myofibroblast differentiation.
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- Amino-protected (R) - 3-amino-piperidine preparation method
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The invention discloses a preparation method of amino protection (R)-3-amino piperidine, and the preparation method comprises the following steps: (1) in the presence of a first solvent or absence of a solvent, reacting a compound of formula V with benzylamine to obtain a compound of formula VI; (2) in the presence of a second solvent, performing catalytic hydrogenation of the compound of formula VI to remove benzyl to obtain the amino protection (R)-3-amino piperidine. According to the method, the defects of use of expensive metal catalysts and use of high-pressure hydrogenation and various splitting for synthesis of a chiral amino piperidine ring can be avoided, at the same time, the synthetic route is short, the process is simple, the yield is high, and the method is suitable for industrial mass production.
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Paragraph 0050-0052
(2017/03/18)
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- (R) - 3-amino-piperidine dihydrochloride preparation method
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The invention discloses a method for preparing (R)-3-amino piperidine hydrochloride. D-glutamic acid is taken as a starting material, and the (R)-3-amino piperidine hydrochloride is obtained by reaction in the following five steps: (1) hydroxyl esterification and amido Boc protection; (2) ester reduction; (3) hydroxyl activation; (4) cyclization; (5) amino Boc removal protection. The preparation method disclosed by the invention is short in synthetic route and low in cost, and industrial production can be achieved.
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- Expeditious synthesis of enantiopure, orthogonally protected bis-α-amino acids (OPBAAs) and their use in a study of Nod1 stimulation
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A convenient approach towards the synthesis of orthogonally protected chiral bis-a-amino acids (OPBAAs) is described. The key transformations include: (1) a highly stereoselective conjugation (alkylation) of the Sch?llkopf bislactim ethers and oxazolidinyl alkyl halides to build a backbone skeleton; and (2) our orthogonal protection strategy. A series of enantiopure OPBAAs bearing a variety of alkyl chain as a spacer; two stereogenic centers; and three protecting groups were prepared as examples. These versatile molecules were applied to the synthesis of biologically interesting di- or tri-peptide analogues, including chiral iE-meso-DAP and A-iE-meso-DAP, for the study of Nod1 activation in the innate immune response.
- Chen, Po-Ting,Lin, Cheng-Kun,Tsai, Chih-Ju,Huang, Duen-Yi,Nien, Fu-Yao,Lin, Wan-Wan,Cheng, Wei-Chieh
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p. 474 - 482
(2015/01/30)
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- PROCESSES OF PREPARING A JAK1 INHIBITOR AND NEW FORMS THERETO
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This invention relates to processes for preparing a JAKl inhibitor having Formula la: as well as new forms of the inhibitor.
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Page/Page column 64; 68; 69
(2015/11/24)
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- TRICYCLIC HETEROCYCLIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF AS JAK INHIBITORS
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The invention provides novel compounds of formula I having the general formula:(I) wherein Rl s R2, R3, X and Y are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.
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- Kilogram synthesis of (S)-3-aminopyran from l -glutamic acid
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We describe the development of a concise route to prepare kilogram quantities of (S)-3-aminopyran, a key intermediate in the synthesis of a Jak1 inhibitor. The chiral amine was introduced via a chiral-pool approach and involves using inexpensive, commerci
- Savage, Scott,Babu, Srinivasan,Zak, Mark,Mao, Zhongping,Cao, Jianhua,Ge, Yonghui,Ma, Dongxu,Jiang, Guoqiang
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p. 987 - 990
(2013/07/05)
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- Catalyst-controlled reversal of chemoselectivity in acylation of 2-aminopentane-1,5-diol derivatives
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Highly chemo- and regioselective acylation of 2-aminopentane-1,5-diol derivatives has been achieved by organocatalysis. An acyl group can be chemoselectively introduced onto the sterically hindered secondary hydroxy group in the presence of the primary on
- Yoshida, Keisuke,Shigeta, Takashi,Furuta, Takumi,Kawabata, Takeo
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supporting information; experimental part
p. 6981 - 6983
(2012/08/07)
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- Asymmetric michael additions of α-nitrocyclohexanone to aryl nitroalkenes catalyzed by natural amino acid-derived bifunctional thioureas
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A series of new thiourea catalysts prepared from natural amino acids have been applied in organocatalytic asymmetric Michael additions of α-nitrocyclohexanone to nitroalkenes. The resulting addition products are formed with excellent enantioselectivities (up to an er of 98:2) in good yields (up to 90%).
- J?rres, Manuel,Schiffers, Ingo,Atodiresei, Iuliana,Bolm, Carsten
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p. 4518 - 4521
(2012/10/29)
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- Synthesis of optically active homotryptophan and its oxygen and sulfur analogues
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d-Homotryptophan and its sulfur analogue have been synthesized by Sonogashira coupling between 3-iodoheteroarenes and ethynyloxazolidine followed by reduction of triple bond and oxidation of alcohol to acid. l-Homotryptophan and its oxygen analogue have b
- Goswami, Koushik,Paul, Sibasish,Bugde, Sandesh T.,Sinha, Surajit
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p. 280 - 286
(2012/01/05)
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- Total synthesis of (-)-indolactam v
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The total synthesis of protein kinase C activator (-)-indolactam V (IL-V) has been successfully completed with two separate approaches: From known 4-nitrotryptophan derivative 3 in 8 steps (49% overall yield) and from l-glutamic acid in 12 steps (18% overall yield), where 4-nitrotryptophanol derivative 4 served as a key intermediate. Derivatives 3 and 4, both incorporating indole 4-substitution and the C-9 stereocenter in IL-V, were synthesized via the Pd-catalyzed indole synthesis from 3-nitro-2-iodoaniline 5 with aldehydes 6 and 7, respectively. Aldehyde 7 was, meanwhile, synthesized from l-glutamic acid in 5 steps (68% yield). Lactamization of the 9-membered ring was achieved using HATU in THF in good yield.
- Xu, Zhengren,Zhang, Fengying,Zhang, Lihe,Jia, Yanxing
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p. 2512 - 2517
(2011/05/06)
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- Synthetic aromatic amino acids from a negishi cross-coupling reaction
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An N,O-protected, iodinated bishomoalanine derivative, safely available from glutamic acid, reacts with aryl halides in a Negishi reaction in high yields. From the coupling product, Fmoc-protected amino acids with aromatic and heteroaromatic side chains were generated in high yields by racemization-free procedures. These monomers could be used for solid-phase peptide synthesis. Georg Thieme Verlag Stuttgart.
- Suhartono, Marcel,Schneider, Angelika E.,Duerner, Gerd,Goebel, Michael W.
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experimental part
p. 293 - 303
(2010/03/30)
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- Hydrogenation of N-acylcarbamates and N-acylsulfonamides catalyzed by a bifunctional [Cp*Ru(PN)] complex
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Awakening of the Cp one: the bifunctional complex 1 facilitates the interaction with substrates bearing less electrophilic carbon atoms than ketones, epoxides, and imides. The title reaction was applicable to the reduction of Evans' asymmetric alkylation products to the chiral alcohols along with gtood recovery of the chiral oxazolidinone auxiliary. EWG=electron- withdrawing group.
- Ito, Masato,Koo, Lee Wei,Himizu, Akio,Kobayashi, Chika,Sakaguchi, Ayaka,Ikariya, Takao
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scheme or table
p. 1324 - 1327
(2009/06/30)
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- 3-(Imidazolyl)-2-aminopropanoic acids
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Compounds according to formula (I) wherein n is 1-4, R1 is optionally substituted C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R2, R3,
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- A stereocontrolled synthetic route to anti-β-amino alcohols
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A physiologically indispensable β-amino hydroxy functionality has been constructed with complete anti-stereoselectivity by intramolecular iodoamidation of (Z)-olefinic homoallylic trichloroacetimidates 4-6, 18, 20, 30 and 32, which comprise bulky substituents at the vinylic positions.
- Kang, Sung Ho,Hwang, Yu Sang,Youn, Joo-Hack
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p. 7599 - 7603
(2007/10/03)
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- Synthesis of a new chiral amine: (S)-5,5-dimethyl-2-methoxymethyl-pyrrolidine
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The title compound, a potential 'quat' auxiliary,was prepared from (S)-glutamic acid derivatives like (S)-N-Benzyl-5-methoxymethyl-2-pyrrolidinone 1. Other routes starting from (S)-pyroglutamic acid in an attempt to bypass N-Aryl compounds like 1 were also tested, but have not rendered the expected results yet.
- Brena-Valle,Cruz-Almanza,Guadarrama-Morales
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p. 697 - 706
(2007/10/03)
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- An efficient conversion of chiral α-amino acids to enantiomerically pure 3-amino cyclic amines
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Enantiomerically pure 3-amino cyclic amines such as 3-amino pyrrolidine, 3-amino piperidine, and 2,3,4,5,6,7-hexahydro-1H-azepine have been synthesized in high yields from the optically active natural α-amino acids such as L-aspartic acid, L-glutamic acid, L-2-aminoadipic acid, and their enantiomers.
- Moon, Sung-Hwan,Lee, Sujin
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p. 3919 - 3926
(2007/10/03)
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- Ortho-substituted benzofused macrocyclic lactams as zinc metalloprotease inhibitors
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The design and preparation of ortho-substituted benzofused macrocyclic lactams are described. The benzofused macrocyclic lactams were designed as neutral endopeptidase 24.11 (NEP) inhibitors. Docking studies were carried out in a model of thermolysin (TLN) using the MACROMODEL and QXP modeling programs to select suitable ring sizes. These studies predicted that the 11- , 12-, and 13-membered ring macrocyclic lactams would be active in both enzymes TLN and NEP. Good predictability of experimental results, within this series, of binding to thermolysin and to a lesser extent to NEP was observed. A visual comparison, docked at the active site of TLN, is presented for thiorphan, a 10-membered ring macrocycle and an 11-membered ring benzofused macrocyclic lactam. Potent inhibition of both NEP and thermolysin was obtained. The 11-membered ring macrocycle 25a is the most potent inhibitor from this series of compounds (TLN IC50 = 68 nM; NEP IC50 = 0.9 nM). The effects of prodrug 44b administered at 10 mg/kg po on plasma atrial natriuretic peptide (ANP) levels in conscious rats was greater than 200% over a 4 h period.
- Ksander, Gary M.,De Jesus, Reynalda,Yuan, Andrew,Ghai,Trapani,McMartin, Colin,Bohacek, Regine
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p. 495 - 505
(2007/10/03)
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- Differential inhibition of aminopeptidase A and aminopeptidase N by new β-amino thiols
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Aminopeptidase A (APA) is a highly selective peptidase, which cleaves the N-terminal Glu or Asp residues of biologically active peptides, and has therefore been proposed to be involved in angiotensin II and CCK8 metabolism. Highly potent and se
- Chauvel,Llorens-Cortes,Coric,Wilk,Roques,Fournie- Zaluski
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p. 2950 - 2957
(2007/10/02)
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