- Stereoselective synthesis of Boc-protected cis and trans-4-trifluoromethylprolines by asymmetric hydrogenation reactions
-
Stereocontrolled synthesis of cis and trans-substituted prolines by a divergent approach, leads to the preparation of cis-(4S)- and trans-(4R)-trifluoromethyl-Lproline from hydroxyproline. The key pyrroline intermediates were subjected to hydrogenation (s
- Del Valle, Juan R.,Goodman, Murray
-
-
Read Online
- Asymmetric synthesis of lycoperdic acid
-
Lycoperdic acid [(2S,5'S)-2-amino-3-(5'-carboxy-2'-oxo-5'- tetrahydrofuranyl)propanoic acid], isolated from the mushroom Lycoperdon perlatum, was synthesized from trans-4-hydroxy-L-proline by a six-step route involving samarium diiodide (SmI2)-mediated formation of the spiro-γ- lactone and ruthenium tetroxide (RuO4) oxidation of the L-proline ring system to the L-pyroglutamic acid moiety. Lycoperdic acid (1) was found to undergo hydrolysis of the γ-lactone ring in 1 N hydrochloric acid at 23°C, giving an equilibrated mixture of 1 and the corresponding hydroxy acid.
- Yoshifuji,Kaname
-
-
Read Online
- γ-(S)-Trifluoromethyl proline: Evaluation as a structural substitute of proline for solid state 19F-NMR peptide studies
-
γ-(4S)-Trifluoromethyl proline was synthesised according to a modified literature protocol with improved yield on a multigram scale. Conformational properties of the amide bond formed by the amino acid were characterised using N-acetyl methyl ester model. The amide populations (s-trans vs. s-cis) and thermodynamic parameters of the isomerization were found to be similar to the corresponding values for intact proline. Therefore, the γ-trifluoromethyl proline was suggested as a structurally low-disturbing proline substitution in peptides for their structural studies by 19F-NMR. Indeed, the exchange of native proline for γ-trifluoromethyl proline in the peptide antibiotic gramicidin S was shown to preserve the overall amphipathic peptide structure. The utility of the amino acid as a selective 19F-NMR label was demonstrated by observing the re-alignment of the labelled gramicidin S in oriented lipid bilayers. This journal is
- Kubyshkin, Vladimir,Afonin, Sergii,Kara, Sezgin,Budisa, Nediljko,Mykhailiuk, Pavel K.,Ulrich, Anne S.
-
-
Read Online
- Synthesis of N-t-Butoxycarbonyl-4,4-dideuterio-L-proline
-
The title compound, which is useful for structural investigations of proline-containing peptides by 1H-N.M.R. spectroscopy, has been synthesized in five simple steps from N-t-butoxycarbonyl-4-hydroxyproline and designed for a maximal deuterium incorporation.The deuterium content was nearly 90percent.
- Dormoy, Jean-Robert,Castro, Bertrand
-
-
Read Online
- VISUAL DETECTION OF PBD INDUCED DNA CROSSLINKS
-
The present invention relates to the field of oncology, laboratory tools and methods, and especially anti-tumor DNA crosslinking agents. Most patients with advanced solid tumors develop resistance to chemotherapy due to the ability of cancer cells to repair or tolerate sustained DNA damages. The inventors showed that the compounds according to the present invention allow the detection and visualization of alkylated DNA damages induced by PBDs without altering their DNA crosslinking ability. This enables the study of the effect and properties of PBDs. In particular, the present invention relates new derivates of PBD molecules and their synthesis. The present invention also relates to a method for visualizing DNA crosslinking; to a method for assessing the resistance of a tumor to a crosslinking agent and to a method for identifying a molecule or treatment for improving the efficiency of a crosslinking agent.
- -
-
Page/Page column 47; 48
(2021/04/23)
-
- NOVEL CONNECTED BODY AND USE THEREOF IN SPECIFIC CONJUGATION BETWEEN BIOMOLECULE AND DRUG
-
PROBLEM TO BE SOLVED: To provide: a method for producing a connected body; a method for using the connected body in the production of a uniform conjugate; and a method for applying the conjugate in the treatment of cancer, infectious diseases, and autoimmune diseases. SOLUTION: A novel connected body is provided that includes a 2,3-di-substituted succinic acid group or a 2-mono-substituted or 2,3-di-substituted fumaric acid or maleic acid (trans (E)- or cis (Z)-butenedioic acid) group for conjugating 2 or more compounds/cytotoxic agents per connected body with a cell-binding molecule by specifically bridge-linking to a pair of thiol on the cell-binding molecule. The connected body is exemplified by the following general formula. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
- -
-
Paragraph 0211-0212
(2021/05/14)
-
- 5-AMINO-8-(4-PYRIDYL)-[1,2,4]TRIAZOLO[4,3-C]PYRIMIDIN-3-ONE COMPOUNDS FOR USE AGAINST CANCER
-
Described herein are triazalone compounds of Formula (I) and pharmaceutically acceptable salts thereof. Methods of making and using compounds of Formula (I) are also described. Compounds of Formula (I) and pharmaceutically acceptable salts thereof can be
- -
-
Page/Page column 75-75
(2021/10/02)
-
- Pyrimidine derivative and application thereof in medicines
-
The invention discloses a pyrimidine derivative and application thereof in medicines, and particularly relates to a novel pyrimidine derivative and a pharmaceutical composition containing the compound. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and application of the compound and the pharmaceutical composition in preparation of drugs for treating KRAS G12C-mediated diseases and/or symptoms, especially in preparation of drugs for treating cancers.
- -
-
Paragraph 0251-0254
(2021/07/21)
-
- CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES
-
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
- -
-
Page/Page column 144
(2020/01/31)
-
- CONJUGATION LINKERS CONTAINING 2,3-DIAMINOSUCCINYL GROUP
-
Provided is a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (adual-linker) containing a 2, 3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.
- -
-
Page/Page column 290
(2020/05/19)
-
- BENZIMIDAZOLE-LINKED INDOLE COMPOUND ACTING AS NOVEL DIVALENT IAP ANTAGONIST
-
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.
- -
-
Paragraph 0272; 0273
(2019/03/14)
-
- Synthesis method of teneligliptin key intermediate
-
The invention discloses a synthesis method of a teneligliptin key intermediate, and relates to the technical field of synthesis, in particular to a synthesis method of a teneligliptin key intermediate(2S)-4-oxo-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester. According to the synthesis method, L-hydroxyproline is subjected to an esterification reaction to obtain a compound 1; the compound 1 is protected by t-butyloxycarboryl to obtain a compound 2; the compound 2 is subjected to an oxidation reaction to obtain a compound 3; the compound 3 and thiazolidine are subjected to an ammonia ester exchange reaction to obtain a compound 4. According to the method, a synthesis route suitable for industrial production is designed aiming at the teneligliptin key intermediate,the complexity of the operation is lowered, expensive dehydration reagents are also avoided, the yield is high, the cost is low, and the synthesis method is suitable for industrial application and popularization.
- -
-
Paragraph 0030-0033
(2019/10/15)
-
- Ni-Catalyzed Arylboration of Unactivated Alkenes: Scope and Mechanistic Studies
-
A method for the Ni-catalyzed arylboration of unactivated monosubstituted, 1,1-disubstituted, and trisubstituted alkenes is disclosed. The reaction is notable in that it converts highly substituted alkenes, aryl bromides, and diboron reagents to products that contain a quaternary carbon and a synthetically versatile carbon-boron bond with control of stereoselectivity and regioselectivity. In addition, the method is demonstrated to be useful for the synthesis of saturated nitrogen heterocycles, which are important motifs in pharmaceutical compounds. Finally, due to the unusual reactivity demonstrated, the mechanistic details of the reaction were studied with both computational and experimental techniques.
- Sardini, Stephen R.,Lambright, Alison L.,Trammel, Grace L.,Omer, Humair M.,Liu, Peng,Brown, M. Kevin
-
supporting information
p. 9391 - 9400
(2019/06/17)
-
- CONJUGATION LINKERS, CELL BINDING MOLECULE-DRUG CONJUGATES CONTAINING THE LIKERS, METHODS OF MAKING AND USES SUCH CONJUGATES WITH THE LINKERS
-
The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.
- -
-
Page/Page column 181; 182
(2018/05/27)
-
- ARYL, HETEROARY, AND HETEROCYCLIC PHARMACEUTICAL COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
-
Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, and Formula V, or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.
- -
-
Page/Page column 645; 646
(2018/09/21)
-
- Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)
-
Bile acid signaling and metabolism in the gastrointestinal tract have wide-ranging influences on systemic disease. G protein-coupled bile acid receptor 1 (GPBAR1, TGR5) is one of the major effectors in bile acid sensing, with demonstrated influence on metabolic, inflammatory, and proliferative processes. The pharmacologic utility of TGR5 agonists has been limited by systemic target-related effects such as excessive gallbladder filling and blockade of gallbladder emptying. Gut-restricted TGR5 agonists, however, have the potential to avoid these side effects and consequently be developed into drugs with acceptable safety profiles. We describe the discovery and optimization of a series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects. The series includes 12 (TGR5 EC50: human, 143 nM; mouse, 1.2 nM), a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.
- Chen, Tao,Reich, Nicholas William,Bell, Noah,Finn, Patricia D.,Rodriguez, David,Kohler, Jill,Kozuka, Kenji,He, Limin,Spencer, Andrew G.,Charmot, Dominique,Navre, Marc,Carreras, Christopher W.,Koo-Mccoy, Samantha,Tabora, Jocelyn,Caldwell, Jeremy S.,Jacobs, Jeffrey W.,Lewis, Jason Gustaf
-
supporting information
p. 7589 - 7613
(2018/09/12)
-
- As hepatitis c inhibitor spiro compound and its use in medicine
-
The invention provides a spiro compound serving as a hepatitis c inhibitor and application thereof in a medicine. The compound is a compound as shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, an aquo-complex, a solvate, a metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in the formula (I). The invention also provides a pharmaceutical composition containing the compound, application of the compound and the pharmaceutical composition in inhibition of HCV (Hepatitis C Virus) copy and HCV virus protein, as well as the application of the compound and the pharmaceutical composition in prevention, handling, treatment or relieving of HCV infection or hepatitis c disease for a patient. The formula I is as shown in the specification.
- -
-
Paragraph 1612; 1621; 1622
(2017/12/28)
-
- HEPATITIS C VIRUS INHIBITORS AND USES THEREOF IN PREPARATION OF DRUGS
-
A series of hepatitis C virus (HCV) inhibitors and compositions and applications thereof in the preparation of drugs for treating chronic HCV infection. Especially, a series of compounds that are used as NS5A inhibitors, and compositions and uses thereof in the preparations of drugs.
- -
-
Paragraph 0320; 0321
(2017/12/17)
-
- Cationic Chiral Fluorinated Oxazaborolidines. More Potent, Second-Generation Catalysts for Highly Enantioselective Cycloaddition Reactions
-
The coordination of chiral ligands to Lewis acid metal derivatives, a useful strategy for enantioselective, electrophilic catalysis, generally leads to a lower level of catalytic activity than that of the original uncomplexed compound. Activation by furth
- Mahender Reddy, Karla,Bhimireddy, Eswar,Thirupathi, Barla,Breitler, Simon,Yu, Shunming,Corey
-
supporting information
p. 2443 - 2453
(2016/03/08)
-
- Aminoheteroaryl benzamides as kinase inhibitors
-
The present invention provides a compound of Formula (I) or a salt thereof; and therapeutic uses of these compounds. The present invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds with a therapeutic co-agent.
- -
-
Page/Page column 75' 76
(2016/02/15)
-
- SPECIFIC CONJUGATION LINKERS, SPECIFIC IMMUNOCONJUGATES THEREOF, METHODS OF MAKING AND USES SUCH CONJUGATES THEREOF
-
The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)- butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.
- -
-
Page/Page column 124-125
(2016/05/24)
-
- NOVEL INDOLE DERIVATIVES AND THEIR USE IN NEURODEGENERATIVE DISEASES
-
The present invention relates to indole compounds, and pharmaceutically acceptable compositions thereof, useful as antagonists of P2X7, and for the treatment of P2X7-related disorders.
- -
-
Paragraph 0869-0870
(2016/11/24)
-
- Bridged Ring compounds As Hepatitis C Virus (HCV) Inhibitors And Pharmaceutical Applications Thereof
-
Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
- -
-
Paragraph 1117; 1118; 1119
(2015/03/28)
-
- NOVEL CYTOTOXIC AGENTS FOR CONJUGATION OF DRUGS TO CELL BINDING MOLECULE
-
Provided are cytotoxic agents, pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives, their conjugates with a cell-binding agent, the preparation and the therapeutic uses in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.
- -
-
Page/Page column 85
(2015/03/16)
-
- NOVEL LINKERS AND THEIR USES IN SPECIFIC CONJUGATION OF DRUGS TO A BIOLOGICAL MOLECULE
-
The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)- butenedioic) group for conjugation of two or more compounds/cytotoxic agents per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.
- -
-
Page/Page column 88
(2015/11/17)
-
- ANTIVIRAL COMPOUNDS
-
The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
- -
-
Paragraph 0336; 0337
(2015/12/31)
-
- SPIRO COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
-
Disclosed are spiro compounds of formula (I), or stereomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof. The compounds can be used to treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore disclosed are pharmaceutical compositions containing the compounds and the method of using the compounds or pharmaceutical compositions in the treatment of HCV infection or hepatitis C disease.
- -
-
Paragraph 0417-0419
(2015/11/09)
-
- BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS (HCV) INHIBITORS AND PHARMACEUTICAL APPLICATIONS THEREOF
-
Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
- -
-
Paragraph 00449
(2014/02/16)
-
- FUSED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided are fused tricyclic compounds effective to inhibit the function of the NS5A protein of formula (I), wherein X, X', Y, Y', A, A',Q1, Q2, R1-R4, X4, R5a, f and W are defined as in the description. Also provided herein are pharmaceutical compositions thereof, and uses in the manufacture of a medicament for treating HCV infection or a HCV disorder thereof.
- -
-
Paragraph 00427; 00428
(2014/06/23)
-
- SPIRO RING COMPOUND AS HEPATITIS C VIRUS (HCV) INHIBITOR AND USES THEREOF FIELD OF THE INVENTION
-
A compound of formula (I) or a stereoisomer, a geometric isomer. a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof is provided, which can be used for treating HCV infection or a HCV disorder. Also a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof are provided, which can also be used for treating HCV infection or a HCV disorder.
- -
-
Page/Page column 158; 159; 160; 161
(2014/06/23)
-
- BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided herein is a compound of formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof, which can also be used for treating HCV infection or a HCV disorder.
- -
-
Page/Page column 124
(2014/09/16)
-
- ANTIVIRAL COMPOUNDS
-
The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
- -
-
Paragraph 0272
(2014/07/08)
-
- HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR TREATMENT OF HEPATITIS C
-
Compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for i
- -
-
Page/Page column 49
(2015/01/16)
-
- HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF HEPATITIS C
-
The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.(I)
- -
-
Page/Page column 46
(2015/01/16)
-
- Extended structure-activity relationship and pharmacokinetic investigation of (4-quinolinoyl)glycyl-2-cyanopyrrolidine inhibitors of fibroblast activation protein (FAP)
-
Fibroblast activation protein (FAP) is a serine protease related to dipeptidyl peptidase IV (DPPIV). It has been convincingly linked to multiple disease states involving remodeling of the extracellular matrix. FAP inhibition is investigated as a therapeutic option for several of these diseases, with most attention so far devoted to oncology applications. We previously discovered the N-4-quinolinoyl-Gly-(2S)-cyanoPro scaffold as a possible entry to highly potent and selective FAP inhibitors. In the present study, we explore in detail the structure-activity relationship around this core scaffold. We report extensively optimized compounds that display low nanomolar inhibitory potency and high selectivity against the related dipeptidyl peptidases (DPPs) DPPIV, DPP9, DPPII, and prolyl oligopeptidase (PREP) the log D values, plasma stabilities, and microsomal stabilities of selected compounds were found to be highly satisfactory. Pharmacokinetic evaluation in mice of selected inhibitors demonstrated high oral bioavailability, plasma half-life, and the potential to selectively and completely inhibit FAP in vivo.
- Jansen, Koen,Heirbaut, Leen,Verkerk, Robert,Cheng, Jonathan D.,Joossens, Jurgen,Cos, Paul,Maes, Louis,Lambeir, Anne-Marie,De Meester, Ingrid,Augustyns, Koen,Van Der Veken, Pieter
-
supporting information
p. 3053 - 3074
(2014/05/06)
-
- NOVEL FAP INHIBITORS
-
The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.
- -
-
Paragraph 0281; 0282; 0283; 0284; 0285
(2014/12/09)
-
- NOVEL FAP INHIBITORS
-
The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.
- -
-
Page/Page column 44
(2013/07/31)
-
- HEPATITIS C VIRUS INHIBITORS
-
The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
- -
-
Paragraph 0471
(2013/05/21)
-
- HETEROCYCLIC COMPOUNDS AND METHODS FOR THEIR USE
-
The present invention relates to heterocyclic compounds useful for antagonising angiotensin II Type 2 (AT2) receptor. More particularly the invention relates to pyrrolidine and azetidine compounds, compositions containing them and their use in methods of treating or preventing disorders or diseases associated with AT2 receptor function including neuropathic pain, inflammatory pain, conditions associated with neuronal hypersensitivity, impaired nerve conduction velocity, cell proliferation disorders, disorders associated with an imbalance between bone resorption and bone formation and disorders associated with aberrant nerve regeneration.
- -
-
Page/Page column 103
(2013/07/19)
-
- NON-SYSTEMIC TGR5 AGONISTS
-
Compounds of structure (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R1, R2, R3, R4, R8, R9, R10, R11, R12, A1, A2, X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.
- -
-
Page/Page column 95
(2013/07/05)
-
- HEPATITIS C VIRUS INHIBITORS
-
The invention provides compounds of formulas (I) or (II): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
- -
-
Paragraph 0242
(2013/11/06)
-
- Synthesis of a novel Boc-protected cyclopropane-modified proline analogue
-
The synthesis of the Boc derivative of a novel member of the cyclopropane-modified proline library, Boc-protected 5-azaspiro[2.4]heptane-6- carboxylic acid, is reported. The synthesis was performed in six steps starting from (2S,4R)-4-hydroxyproline using a modified Simmons-Smith reaction as the key step. The reaction conditions for all the steps were carefully selected to avoid racemization at the chiral centers in the intermediates and the final product.
- Tymtsunik, Andriy V.,Bilenko, Vitaliy A.,Ivon, Yevhen M.,Grygorenko, Oleksandr O.,Komarov, Igor V.
-
scheme or table
p. 3847 - 3849
(2012/08/27)
-
- A Diels-Alder-based total synthesis of (-)-kainic acid
-
An efficient synthesis of (-)-kainic acid, through a high-pressure-promoted Diels-Alder cycloaddition of a vinylogous malonate derived from 4-hydroxyproline, is described. The bicyclic adduct could be converted into the natural product with complete stereocontrol.
- Orellana, Arturo,Pandey, Sushil K.,Carret, Sebastien,Greene, Andrew E.,Poisson, Jean-Francois
-
scheme or table
p. 5286 - 5296
(2012/08/27)
-
- 3,4-DIHYDRO-PYRROLO[1,2-a]PYRAZIN-1-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)
-
The present invention relates to novel 3,4-dihydro-pyrrolo[l,2-a]pyrazin-1-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.
- -
-
Page/Page column 39
(2012/09/22)
-
- METABOTROPIC GLUTAMATE RECEPTORS 5 MODULATORS AND METHODS OF USE THEREOF
-
Compounds that modulate GluR5 activity and methods of using the same are disclosed.
- -
-
Page/Page column 152
(2012/12/13)
-
- SAR development of lysine-based irreversible inhibitors of transglutaminase 2 for huntington's disease
-
We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.
- Wityak, John,Prime, Michael E.,Brookfield, Frederick A.,Courtney, Stephen M.,Erfan, Sayeh,Johnsen, Siw,Johnson, Peter D.,Li, Marie,Marston, Richard W.,Reed, Laura,Vaidya, Darshan,Schaertl, Sabine,Pedret-Dunn, Anna,Beconi, Maria,MacDonald, Douglas,Mu?oz-Sanjuan, Ignacio,Dominguez, Celia
-
supporting information
p. 1024 - 1028
(2013/02/22)
-
- Part 3: Design and synthesis of proline-derived α2δ ligands
-
A potent series of substituted (2S,4S)-benzylproline α 2δ ligands have been designed from the readily available starting material (2S,4R)-hydroxy-l-proline. The ligands have improved pharmacokinetic profile over the (4S)-phenoxyproline derivati
- Rawson, David J.,Brugier, Delphine,Harrison, Anthony,Hough, Jo,Newman, Julie,Otterburn, Joe,Maw, Graham N.,Price, Jenny,Thompson, Lisa R.,Turnpenny, Paul,Warren, Andrew N.
-
scheme or table
p. 3771 - 3773
(2011/08/06)
-
- Design, synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives as novel peptide deformylase inhibitors
-
The synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated to discover SAR at P1′ and P 3′ positions, and most of
- Shi, Wei,Ma, Haikun,Duan, Yuejiao,Aubart, Kelly,Fang, Yuhong,Zonis, Rimma,Yang, Liping,Hu, Wenhao
-
scheme or table
p. 1060 - 1063
(2011/03/21)
-
- CHEMICAL COMPOUNDS
-
Disclosed are compounds of Formula (I). Also disclosed are pharmaceutical compositions comprising the compounds, and methods for treating HCV invention by administration of the compounds.
- -
-
Page/Page column 45
(2011/05/06)
-
- ANTI-VIRAL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE
-
Disclosed are compounds, stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, their preparation, use, and compositions thereof for treating an infection mediated at least in part by a virus in the Flaviviridae family of viruses.
- -
-
Page/Page column 58
(2010/06/17)
-
- Remarkable enhancement in the DNA-binding ability of C2-fluoro substituted pyrrolo[2,1-c][1,4]benzodiazepines and their anticancer potential
-
C2-Fluoro substituted DC-81, and its dimers that comprise of two C2-fluoro substituted DC-81 subunits tethered to their C8-position through simple alkane spacers as well as piperazine moiety side-armed with symmetrical alkyloxy spacers have been designed
- Kamal, Ahmed,Rajender,Reddy, D. Rajasekhar,Reddy, M. Kashi,Balakishan,Shaik, T. Basha,Chourasia, Mukesh,Sastry, G. Narahari
-
experimental part
p. 1557 - 1572
(2009/08/15)
-
- A novel approach to 2,4-ethanoproline
-
A novel approach to 2-azabicyclo[2.2.1]heptane-1-carboxylic acid (2,4-ethanoproline) is reported starting from (2S,4R)-4-hydroxyproline. The synthetic scheme consists of 10 steps and results in 22% total yield of the title compound. Enantiomeric purity of the product is checked by chiral stationary phase HPLC.
- Grygorenko, Oleksandr O.,Komarov, Igor V.,Cativiela, Carlos
-
experimental part
p. 1433 - 1436
(2009/12/03)
-
- 1,3-Dihydro-2H-Indole-2-One Compound and Pyrrolidine-2-One Compound Fused With Aromatic Heterocycle
-
It is intended to provide a drug which is efficacious against pathological conditions relating to arginine-vasopressin V1b receptor. More particularly speaking, it is intended to provide a drug which has a therapeutic or preventive effect on depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug addiction, epilepsy, brain infarction, brain ischemia, brain edema, head injury, inflammation, immune diseases, alopecia and so on. As the results of intensive studies, a novel 1,3-dihydro-2H-indol-2-one compound and a pyrrolidin-2-one compound fused with a heteroaromatic ring, which are highly selective antagonists of arginine-vasopressin V1b receptor, have high metabolic stabilities and show favorable brain penetration and high plasma concentrations, are found, thereby achieving the above objective.
- -
-
Page/Page column 60
(2009/01/24)
-