- Highly diastereoselective alkylation of a pyroglutamate derivative with an electrophile obtained from indole. Synthesis of a potential intermediate for the preparation of the natural sweetener (-)-Monatin
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The synthesis of a potential intermediate for the preparation of the very intensive sweetening agent (-)-Monatin is described. The synthesis is based on a highly diastereoselective alkylation reaction of a pyroglutamate derivative with an electrophile obtained from indole.
- Oliveira, Davi De Jesus,Coelho, Fernando
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Read Online
- INHIBITORS OF APOL1 AND METHODS OF USING SAME
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The disclosure provides at least one entity chosen from compounds of formula (I), solid state forms of the same, compositions comprising the same, and methods of using the same, including use in treating focal segmental glomerulosclerosis (FSGS) and/or non-diabetic kidney disease (NDKD).
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- ANTIMICROBIAL COMPOUNDS AND METHODS
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The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
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Paragraph 00715
(2020/07/31)
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- BENZIMIDAZOLE-LINKED INDOLE COMPOUND ACTING AS NOVEL DIVALENT IAP ANTAGONIST
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The present invention discloses a benzimidazole-linked indole compound acting as novel divalent IAP antagonist, specifically disclosing the compound shown in fomulas (I) or a pharmaceutically acceptable salt thereof.
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Paragraph 0305; 0306
(2019/03/14)
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- ANTI-EGFR ANTIBODY DRUG CONJUGATES
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The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs.
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Paragraph 1175
(2019/06/07)
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- NITROGEN-CONTAINING HETEROCYCLIC AMIDE COMPOUND AND PHARMACEUTICAL USE THEREOF
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PROBLEM TO BE SOLVED: To provide a nitrogen-containing heterocyclic amide compound having pyruvate dehydrogenase kinase inhibitory activity, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the same. SOLUTION: The present invention provides a compound of formula [I-a] or formula [II], or a pharmaceutically acceptable salt thereof (a bond of a dotted line: a single bond or a double bond. X1: C, N, O. X2: C, N. R1a: C1-4 alkyl, C1-4 alkyl carbonyl. R2: halogen, cyano, C1-4 alkyl. A1-A7: C, N, O. A8: C, N. R3, R4: H, C1-4 alkyl. Cy1: C4-6 cycloalkyl or the like. Cy2: C3-6 cycloalkyl or the like. m, t, w: 0, 1. n, r, v: 0, 1, 2.) SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
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Paragraph 0463-0465
(2019/08/29)
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- Compounding method for LCZ696 midbody
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The invention discloses a compounding method for a LCZ696 midbody. The compounding route is as follows: wherein R1 is Me, Et or i-Pr; X is Cl, Br or I; R2 is Ms, Ts or Tf. According to the compounding method for the LCZ696 midbody disclosed by the invention, the methylating difficulty is reduced, the midbody is configured and overturned through the consequent reaction, the proportion of the required configuration is greatly increased, the product yield, purity and use ratio are increased and the industrial large-scale production is benefited.
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- Method for preparing hydrobromic acid teneligliptin
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The invention provides a method for preparing hydrobromic acid teneligliptin. The method includes steps of preparing L-hydroxyproline; mixing the L-hydroxyproline and sodium bicarbonate with each other to obtain mixtures, dissolving the mixtures in water, adding acetone into the water, dropping di-tert-butyl dicarbonate into the water, carrying out room-temperature reaction overnight and then treating reaction products to obtain t-butyloxycarboryl-N-hydroxyproline; preparing t-butyloxycarboryl-N-4-oxo-proline from the t-butyloxycarboryl-N-hydroxyproline; preparing (2S)-4-oxo-2-(3-thiazolidine carbonyl)-1-pyrrolidine carboxylic acid tert-butyl ester from the t-butyloxycarboryl-N-4-oxo-proline; preparing compounds III from compounds IV; preparing compounds II from the compounds III; preparing compounds 1-(3-methyl-1-phenyl-1H-pyrazole-5-base) piperazine from the compounds II; preparing intermediates I; preparing the hydrobromic acid teneligliptin from the intermediates I. The method has the advantages that the method is low in cost, and the cost of the method is only two-thirds of the cost of an existing method in the prior art; the yield of the hydrobromic acid teneligliptin is higher than 95%, and the purity of the hydrobromic acid teneligliptin is higher than 98%.
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- ANTI-CD98 ANTIBODIES AND ANTIBODY DRUG CONJUGATES
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The invention relates to anti-CD98 antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.
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Page/Page column 482
(2018/01/15)
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- ANTI-EGFR ANTIBODY DRUG CONJUGATES
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The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs.
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Page/Page column 430; 431
(2018/01/15)
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- ANTI-CD98 ANTIBODIES AND ANTIBODY DRUG CONJUGATES
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The invention relates to anti-CD98 antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.
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Page/Page column 614-615
(2018/01/17)
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- ANTI-EGFR ANTIBODY DRUG CONJUGATES
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The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs. Formula (IIa), (IIb), (IIc)
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Page/Page column 573
(2018/01/17)
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- ANTI-CD98 ANTIBODIES AND ANTIBODY DRUG CONJUGATES
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The invention relates to anti-CD98 antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.
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Page/Page column 374
(2018/01/15)
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- ANTI-B7-H3 ANTIBODIES AND ANTIBODY DRUG CONJUGATES
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The invention relates to B7 homology 3 protein (B7-H3) antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.
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Paragraph 2059
(2018/01/13)
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- Preparation method for L-hydroxyproline
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The invention provides a preparation method for L-hydroxyproline. The preparation method comprises the following steps: preparing pyroglutamic acid; preparing pyroglutamate; preparing pyroglutamic acid alcohol; preparing (3R,7aS)-3-phenyltetrahydropyrrolo[1,2]oxazole-5(3H)-one; and preparing L-hydroxyproline. Compared with the prior art, the invention has the following beneficial effects: the method overcomes the problems that a traditional manner of extraction of L-hydroxyproline from an animal donor has potential safety hazards and that production of L-hydroxyproline is limited as biological raw materials are utilized, and can synthesize L-hydroxyproline under the condition of shortage of biological raw materials; synthetic methods for L-hydroxyproline are enriched; the added value of L-hydroxyproline is increased; the application scope of L-hydroxyproline can be further broadened; prepared L-hydroxyproline is high in yield and purity, so the synthesis purity of atazanavir is indirectly improved; and common raw materials can be selected in preparation of L-hydroxyproline, so production cost is low.
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- BCL-XL Inhibitory Compounds and Antibody Drug Conjugates Including the Same
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Small molecule Bcl-xL inhibitors and Antibody Drug Conjugates (ADCs) comprising small molecule Bcl-xL inhibitors are disclosed herein. The Bcl-xL inhibitors and ADCs of the disclosure are useful for, among other things, inhibiting anti-apoptotic Bcl-xL proteins as a therapeutic approach towards the treatment of diseases that involve a dysregulated apoptosis pathway.
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Paragraph 1068
(2016/06/28)
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- BCL XL INHIBITORY COMPOUNDS HAVING LOW CELL PERMEABILITY AND ANTIBODY DRUG CONJUGATES INCLUDING THE SAME
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The present disclosure concerns Bcl-xL inhibitors having low cell permeability, antibody drug conjugates (ADCs) comprising the inhibitors, synthons useful for synthesizing the ADCs, compositions comprising the inhibitors or ADCs, and various methods of using the inhibitors and ADCs.
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Paragraph 0001080
(2016/07/05)
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- Application of Two Direct C(sp3)-H Functionalizations for Total Synthesis of (+)-Lactacystin
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(Figure Presented). Herein, we report a new synthetic route from (S)-pyroglutaminol to (+)-lactacystin, a potent inhibitor of the 20S proteasome. The photoinduced intermolecular C(sp3)-H alkynylation and intramolecular C(sp3)-H acylation chemo- and stereoselectively constructed the tetra- and trisubstituted carbon centers, respectively. The obtained bicycle was transformed into the target compound in a concise manner. The present total synthesis demonstrates the power of the direct C(sp3)-H functionalizations for the assembly of multiple functionalized structures of natural products.
- Yoshioka, Shun,Nagatomo, Masanori,Inoue, Masayuki
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supporting information
p. 90 - 93
(2015/07/28)
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- Anti-Beckwith stereoselectivity in amidyl radical cyclisations: Bu 3SnH-mediated 5-exo-trig acyl mode cyclisation of 2-substituted pent-4-enamide radicals
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2-Substituted amidyl radicals derived from 8a-d and 9a-d undergo acyl mode 5-exo-trig cyclisation to give 3,5-trans pyrrolidinones 11a-d and 14a-d as the major products in low diastereoselectivity (de = 9-36%). The steric nature of the nitrogen substituent attached to the amidyl radical does not have a significant effect on selectivity. The stereochemical outcome is opposite to that expected based upon applying the Beckwith rule.
- Clark, Andrew J.,Filik, Robert P.,Thomas, Gerard H.,Sherringham, John
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p. 4094 - 4097
(2013/07/26)
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- PROCESSES FOR THE PREPARATION OF NOVEL BENZIMIDAZOLE DERIVATIVES
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The present invention relates to processes and intermediates for the preparation of novel benzimidazole derivatives, especially in the synthesis of hepatits C virus NS5A inhibitors. In particular, the present invention relates to processes and intermediates for the preparation of compounds of formulae (I-a):
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Page/Page column 25
(2013/05/09)
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- Synthesis of 3-guaninyl- and 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone nucleosides
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l- And d-glutamic acids, as well as trans-4-hydroxy-l-proline, are converted to the corresponding 3-guaninyl-5-hydroxymethyl-2-pyrrolidinone (4) or 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone (5) nucleoside analog. The protecting group used to block the lactam nitrogen in key intermediates has a significant effect on the diastereoselectivity of the coupling reaction with adenine or guanine.
- Saleh, Abdullah,D'Angelo, John G.,Morton, Martha D.,Quinn, Jesse,Redden, Kendra,Mielguz, Rafal W.,Pavlik, Christopher,Smith, Michael B.
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p. 5574 - 5583
(2011/10/02)
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- Alternative route towards the convergent synthesis of a human purine nucleoside phosphorylase inhibitor-forodesine HCl
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Forodesine HCl is being investigated as a potential target for the control of T-cell proliferation. Herein we present an alternative route for the synthesis of the target molecule with addition of lactam to the lithiated deazahypoxanthine (generated in situ). The lactam was synthesized in five steps starting from l-pyroglutamic acid.
- Kamath, Vivekanand P.,Xue, Jie,Juarez-Brambila, Jesus J.,Morris Jr., Philip E.
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scheme or table
p. 5198 - 5200
(2009/12/06)
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- SPIROPYRROLIDINES AND THEIR USE AGAINST HCV AND HIV INFECTION
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The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of human diseases.
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Page/Page column 126
(2009/05/30)
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- ALTERNATIVE SYNTHESIS OF RENIN INHIBITORS AND INTERMEDIATES THEREOF
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The present invention relates to synthetic routes to prepare a compound of the formula (A); wherein R1 is halogen, C1-6 halogenalkyl, C1-6 alkoxy-C1-6 alcoxy or C1-6alkoxy-C1-6alkyl; R2 is halogen, C1-4alkyl or C1-4alkoxy; R3 and R4 are independently branched C3-6alkyl; and R5 is cycloalkyl, C1-6alkyl, C1-6hydroxyalkyl, Cl-6alkoxy-C 1-6alkyl, C1-6alkanoyloxy-C1-6alkyl, C1-6aminoalkyl, C1-6alkylamino-C 1-6alkyl, Cl-6dialkylamino-C1-6alkyl, C1-6alkanoylamino- C1-6alkyl, HO(O)C-Cl-6alkyl, C1-6alkyl-O-(O)C-C1-6alkyl, H2N-C(O)-Cl-6alkyl, C1-6alkyl-HN-C(O)-C1-6alkyl or (C1-6alkyl)2N-C(O)-C1-6alkyl; or a pharmaceutically acceptable salt thereof as well as key intermediates obtained when following these routes as well as their preparation.
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Page/Page column 7; 38
(2010/10/20)
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- VLA-4 INHIBITORS
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The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.
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- Total synthesis of (+)-calyculin A and (-)-calyculin B: Cyanotetraene construction, asymmetric synthesis of the C(26-37) oxazole, fragment assembly, and final elaboration
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A convergent total synthesis leading to (+)-calyculin A and (-)-calyculin B (1 and 2), antipodes of the potent, highly selective and remarkably cell-permeable phosphatase inhibitors calyculins A and B, has been achieved. In the preceding paper we outlined the asymmetric synthesis of the C(9-25) spiroketal dipropionate subunit (+)-BC; herein we describe construction of the C(1-8) cyanotetraene, an asymmetric synthesis of the C(26-37) oxazole, fragment assembly and final elaboration to (+)-1 and (-)-2. Highlights of the synthesis include: application of a one-pot three-component Suzuki reaction for the construction of phosphonate A, a bifunctional triene precursor of the light sensitive C(1-8) cyanotetraene subunit, an asymmetric synthesis of the C(26-32) oxazole (-)-D, exploiting the Silks-Odom 77Se NMR protocol to assess enantiomeric purity, construction of the C(33-37) subtarget (-)-E in a highly stereocontrolled fashion via an acyliminium ion, and a concise, highly efficient sequence for fragment assembly and elaboration to (+)-calyculin A and (-)-calyculin B. The synthesis of (-)-2 also confirms the structure of calyculin B, previously based only on spectral comparison with calyculin A.
- Smith III, Amos B.,Friestad, Gregory K.,Barbosa, Joseph,Bertounesque, Emmanuel,Duan, James J.-W.,Hull, Kenneth G.,Iwashima, Makoto,Qiu, Yuping,Spoors, P. Grant,Salvatore, Brian A.
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p. 10478 - 10486
(2007/10/03)
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- Functionalised pyrrolidinones derived from (S)-pyroglutamic acid
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The generation of the lactam enolate derived from bicyclic lactams 2a-c, prepared from (S)-pyroglutamic acid 1a, and subsequent reaction with a range of electrophiles, is reported. Exo-diastereoselectivity is generally favoured. The deprotection of some of these adducts to give functionalised hydroxymethylpyrrolidinones is readily achieved by simple hemiaminal ether cleavage under acidic conditions.
- Beard, Mark J.,Bailey, Jonathan H.,Cherry, David T.,Moloney, Mark G.,Shim, Sung Bo,Statham, Kathryn A.,Bamford, Mark J.,Lamont, R. Brian
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p. 3719 - 3740
(2007/10/03)
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- A MESO SPECIFIC REACTION
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Acid-catalyzed condensation of optically pure 5-(hydroxymethyl)-2-pyrrolidinone, 2, with benzaldehyde gives only a monomeric optically active oxazolidine, 3, while under the same conditions, racemic 2 gives only a meso centrosymmetric compound 4 - a dimer of racemic 3.This meso specific reaction serves as a highly efficient method for increasing the optical purity of the generally useful chiral building blocks 2 and 3.
- Thottathil, John K.,Przybyla, Claire,Malley, Mary,Gougoutas, J. Z.
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p. 1533 - 1536
(2007/10/02)
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