- Multi-arm polymeric prodrug conjugates of pemetrexed-based compounds
-
Among other aspects, provided herein are multi-arm polymeric prodrug conjugates of pemetrexed-based compounds. Methods of preparing such conjugates as well as methods of administering the conjugates are also provided. Upon administration to a patient, release of the pemetrexed-based compound is achieved.
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Page/Page column 43; 44; 45
(2020/08/30)
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- Structure-based design, synthesis and bioactivity evaluation of macrocyclic inhibitors of mutant isocitrate dehydrogenase 2 (IDH2) displaying activity in acute myeloid leukemia cells
-
The enzymes involved in the metabolic pathways in cancer cells have been demonstrated as important therapeutic targets such as the isocitrate dehydrogenase 2 (IDH2). A series of macrocyclic derivatives was designed based on the marketed IDH2 inhibitor AG-221 by using the conformational restriction strategy. The resulted compounds showed moderate to good inhibitory potential against different IDH2-mutant enzymes. Amongst, compound C6 exhibited better IDH2R140Q inhibitory potency than AG-221, and showed excellent activity of 2-hydroxyglutarate (2-HG) suppression in vitro and its mesylate displayed good pharmacokinetic profiles. Moreover, C6 performed strong binding mode to IDH2R140Q after computational docking and dynamic simulation, which may serve as a good starting point for further development.
- Che, Jinxin,Chen, Binhui,Dong, Xiaowu,Gao, Anhui,Gao, Jian,Hu, Xiaobei,Hu, Yongzhou,Huang, Feng,Li, Jia,Qu, Bingxue,Xu, Gaoya,Ying, Huazhou,Zhang, Jianjun,Zhang, Mengmeng,Zhou, Yubo
-
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- QUINOLINE AND QUINAZOLINE COMPOUNDS AND METHODS OF USE THEREOF
-
Compounds and methods for their preparation and use as therapeutic or prophylactic agents, fo example for treatment of cancer, bacterial or viral diseases by targeting Ectonucleotide Pyrophosphatase/Phosphodiesterase- 1 (ENPP1).
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Paragraph 00453-00454
(2020/10/09)
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- NON-FUSED TRICYCLIC COMPOUNDS
-
Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for treating cancers. Specific cancers include those that are mediated by YAP/TAZ or those that are modulated by the interaction between YAP/TAZ and TEAD.
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Paragraph 00671
(2018/11/26)
-
- CHEMICAL BLOWING AGENT AND THERMALLY EXPANDABLE THERMOPLASTIC COMPOSITION
-
The present invention relates to a chemical blowing agent comprising at least one tertiary alkyl carbamate. The chemical blowing agent can be activated thermally and is suitable for foaming thermoplastic materials and can for example be incorporated into thermally expandable baffle and/or reinforcement elements which are used in automotive manufacturing and building insulation.
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Page/Page column 27; 28; 29
(2016/07/05)
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- POLYFLUORINATED COMPOUNDS ACTING AS BRUTON TYROSINE KINASE INHIBITORS
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Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.
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Paragraph 0779; 0780
(2016/08/17)
-
- TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE
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Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.
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Paragraph 0768; 0769
(2016/12/22)
-
- ANTHRACYCLINE DISULFIDE INTERMEDIATES, ANTIBODY-DRUG CONJUGATES AND METHODS
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The invention provides antibody-drug conjugates comprising an antibody conjugated to an anthracycline drug moiety via a disulfide linker, anthracycline disulfide intermediates, and methods of using the antibody-drug conjugates.
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Paragraph 0324-0326; 0330
(2016/04/09)
-
- NOVEL CONDENSED PYRAZOLE DERIVATIVE AND MEDICAL USES THEREOF
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PROBLEM TO BE SOLVED: To provide a preventive or therapeutic agent for mood disorder, anxiety disorder, schizophrenia, dementia, drug dependence or the like related to subtypes of metabolism type glutamate receptor (mGlu) 2 and 3. SOLUTION: There are prov
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Paragraph 0270; 0271
(2016/10/10)
-
- Synthesis of substituted imidazolines by an Ugi/Staudinger/aza-Wittig sequence
-
A series of 2-(acetamide-2-yl)-imidazolines (II) with 5 points of diversity were prepared by an Ugi-4CR-Staudinger-aza-Wittig-sequence starting from simple azidoalkylamines. The intramolecular aza-Wittig cyclization between the iminophosphane and the tertiary amide of the Ugi product (I) was effected by short microwave irradiation. Competitive cyclization to the secondary amide was not relevant, however, in some cases subsequent formation of the bicyclic ortho-amidines (III) was observed.
- Welsch, Sebastian J.,Umkehrer, Michael,Kalinski, Cedric,Ross, Günther,Burdack, Christoph,Kolb, Jürgen,Wild, Martina,Ehrlich, Anja,Wessjohann, Ludger A.
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supporting information
p. 1025 - 1029
(2015/02/19)
-
- AZEPANE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS
-
Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
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Paragraph 0744; 0745; 0746
(2015/07/22)
-
- Hexahydro-1 H -Isoindolinone-Like Scaffolds from Electronically Deactivated and Sterically Hindered Dienes: Synthesis in the Context of Muironolide A
-
Initial synthetic efforts toward muironolide A based upon an intramolecular Diels-Alder strategy were hampered by a conjugate reduction rather than the desired half-reduction. An intermolecular Diels-Alder strategy was initiated that utilized electronically deactivated and sterically hindered dienes. The [4+2] cycloadditions were successful, but only with highly reactive dipolarophiles such as N-phenylmaleimide and 4-phenyl-1,2,4-triazoline-3,5-dione thus establishing the scope of these dienes. Although limited, installation of the α,β-unsaturated lactam embedded in the hexahydro-1H-isoindolinone is noteworthy.
- Olson, Christopher A.,Shaner, Courtnay E.,Roche, Sydney C.,Ferrence, Gregory M.,Mitchell, T. Andrew
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p. 2756 - 2766
(2015/09/15)
-
- AZEPANE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS
-
Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
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-
Paragraph 0740
(2015/09/22)
-
- Methyl-substitution of an iminohydantoin spiropiperidine β-secretase (BACE-1) inhibitor has a profound effect on its potency
-
The IC50 of a beta-secretase (BACE-1) lead compound was improved ~200-fold from 11 μM to 55 nM through the addition of a single methyl group. Computational chemistry, small molecule NMR, and protein crystallography capabilities were used to com
- Egbertson, Melissa,McGaughey, Georgia B.,Pitzenberger, Steven M.,Stauffer, Shaun R.,Coburn, Craig A.,Stachel, Shawn J.,Yang, Wenjin,Barrow, James C.,Neilson, Lou Anne,McWherter, Melody,Perlow, Debra,Fahr, Bruce,Munshi, Sanjeev,Allison, Timothy J.,Holloway, Katharine,Selnick, Harold G.,Yang, Zhiqiang,Swestock, John,Simon, Adam J.,Sankaranarayanan, Sethu,Colussi, Dennis,Tugusheva, Katherine,Lai, Ming-Tain,Pietrak, Beth,Haugabook, Shari,Jin, Lixia,Chen,Holahan, Marie,Stranieri-Michener, Maria,Cook, Jacquelynn J.,Vacca, Joseph,Graham, Samuel L.
-
supporting information
p. 4812 - 4819
(2015/10/28)
-
- 6,7-DIHYDROPYRAZOLO[1,5-a]PYRAZIN-4(5H)-ONE COMPOUNDS AND THEIR USE AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
-
The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives of Formula (I) as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 ("mGluR2"). 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 or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved, especially CNS disorders.
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Page/Page column 79
(2015/01/06)
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- NOVEL SYNTHETIC PROCESS TO 8-CHLORO-1-METHYL-BENZO[D]AZEPINE, NOVEL INTERMEDIATES AND THE PRODUCTION THEREOF
-
The present invention is directed to a simple and economical process for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine via novel intermediates and a highly selective asymmetric synthesis leading to enantiopure (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d] azepine or its (S)-enantiomer, in order to avoid or overcome chemical optical resolution.
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Page/Page column 52; 53
(2014/11/13)
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- SnAP reagents for the synthesis of piperazines and morpholines
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Substituted piperazines and morpholines are valuable structural motifs in biologically active compounds, but are not easily prepared by contemporary cross-coupling approaches. In this report, we introduce SnAP reagents for the transformation of aldehydes into N-unprotected piperazines and morpholines. This approach offers simple, mild conditions compatible with aromatic, heteroaromatic, aliphatic, and glyoxylic aldehydes and provides mono- and disubstituted N-heterocycles in a single step.
- Luescher, Michael U.,Vo, Cam-Van T.,Bode, Jeffrey W.
-
supporting information
p. 1236 - 1239
(2014/03/21)
-
- FATTY ACID ACETYLATED SALICYLATES AND THEIR USES
-
The invention relates to Fatty Acid Acetylated Salicylate Derivatives; compositions comprising an effective amount of a Fatty Acid Acetylated Salicylate Derivative; and methods for treating or preventing an inflammatory disorder comprising the administration of an effective amount of a Fatty Acid Acetylated Salicylate Derivative.
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Page/Page column 122
(2010/03/04)
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- QUINAZOLINE DERIVATIVES AS A MULTIPLEX INHIBITOR AND METHOD FOR THE PREPARATION THEREOF
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The present invention relates to a novel quinazoline derivative and a pharmaceutically acceptable salt thereof as a multiplex inhibitor, a method for the preparation thereof, and a pharmaceutical composition and a therapeutic composition comprising same as an active ingredient. The inventive quinazoline derivative as a multiplex inhibitor can selectively and effectively inhibit diseases caused by the overactivity of a tyrosine kinase.
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Page/Page column 95
(2008/06/13)
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- Thienopyrimidines useful as Aurora kinase inhibitors
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The present invention provides compounds having the formula: wherein R1, R2, X1, X2, L1, L2, Y and Z are as defined in classes and subclasess herein, and pharmaceutical compositions thereof, as described generally and in subclasses herein, which compounds are useful as inhibitors of protein kinase (e.g., Aurora), and thus are useful, for example, for the treatment of Aurora mediated diseases.
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Page/Page column 108
(2008/06/13)
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- DIPEPTIDYL PEPTIDASE-IV INHIBITING COMPOUNDS, METHODS OF PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE AGENT
-
The present invention relates to novel compounds exhibiting good inhibitory activity versus Dipeptidyl Peptidase-IV(DPP-IV), methods of preparing the same and pharmaceutical compositions containing the same as an active agent.
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Page/Page column 27
(2010/11/24)
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- A modular system for the preparation of diazirine-labeled mannose derivatives using thiourea bridging
-
The protein FimH is a bacterial lectin, which is utilized by Escherichia coli to adhere to the glycocalyx of potential host cells. FimH has specificity for α-mannosyl residues, as revealed by biological as well as X-ray studies. To further investigate the
- Walter, Mark,Lindhorst, Thisbe K.
-
p. 952 - 958
(2007/10/03)
-
- SPIROPIPERIDINE COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHERMER’S DISEASE
-
The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. T
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Page/Page column 97; 98
(2010/11/08)
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- The synthesis of a monoammonium derivative of fullerenopyrrolidine
-
The Prato reaction was used to synthesize a monoammonium derivative of fullerenopyrrolidine.
- Kutyreva,Shchupak,Karnatsevich,Bazyakina,Suvorova
-
p. 1535 - 1536
(2007/10/03)
-
- Enantioselective synthesis of β-hydroxy amines and aziridines using asymmetric transfer hydrogenation of α-amino ketones
-
Enantioselective transfer hydrogenation of α-amino ketones is an effective method for the asymmetric synthesis of β-hydroxy amines and aziridines.
- Kawamoto,Wills
-
p. 1916 - 1928
(2007/10/03)
-
- Di-tert-butyl dicarbonate and 4-(dimethylamino)pyridine revisited. Their reactions with amines and alcohols
-
The reaction of BOC2O in the presence and absence of DMAP was examined with some amines, alcohols, diols, amino alcohols, and aminothiols. Often, unusual products were observed depending on the ratio of reagents, reaction time, polarity of solvent, pK(a) of alcohols, or type of amine (primary or secondary). In reactions of aliphatic alcohols with BOC2O/DMAP, we isolated for the first time carbonic-carbonic anhydride intermediates; this helps explain the formation of symmetrical carbonates in addition to the O-BOC products. In the case of secondary amines, we succeeded to isolate unstable carbamic-carbonic anhydride intermediates that in the presence of DMAP led to the final N-BOC product. The effect of N-methylimidazole in place of DMAP was also examined.
- Basel, Yochai,Hassner, Alfred
-
p. 6368 - 6380
(2007/10/03)
-
- Syntheses of amino nitrones. Potential intramolecular traps for radical intermediates in monoamine oxidase-catalyzed reactions
-
Monoamine oxidase (MAO) is a flavin-dependent enzyme that catalyzes the oxidative deamination of a variety of amine neurotransmitters and toxic amines. Although there have been several studies that support the intermediacy of an amine radical cation and a
- Zhong, Boyu,Lu, Xingliang,Silverman, Richard B.
-
p. 2405 - 2419
(2007/10/03)
-
- Arylamidoalkyl-N-hydroxyurea compounds having lipoxygenase inhibitory activity
-
The present invention provides certain (substituted carbocyclic aryl)amidoalkyl- and (substituted heterocyclic aryl)amidoalkyl-N-Hydroxy urea compounds which inhibit lipoxygenase enzyme activity and are thus useful in the treatment of allergic and inflammatory disease states.
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-
-
- Acylation and alkoxycarbonylation of oximes through an enzymatic oximolysis reaction
-
Ketone or benzaldehyde O-acyloximes and O-(tert-butoxycarbonyl)oximes can be prepared by reaction of oximes with vinyl esters and di-tert-butyl dicarbonate, respectively, using lipases as biocatalysts.
- Menendez,Gotor
-
-
- ARYLAMIDOALKYL-N-HYDROXYUREA COMPOUNDS HAVING LIPOXYGENASE INHIBITORY ACTIVITY
-
The present invention provides certain (substituted carbocyclic aryl)amidoalkyl and (substituted hetero cyclic aryl) amido alkyl-N-Hydroxy urea compounds which inhibit lipoxygenase enzyme activity and are thus useful in the treatment of allergic and inflammatory disease states
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-
-
- SYNTHESIS OF 1,2-AMINOAZIDES. CONVERSION TO UNSYMMETRICAL VICINAL DIAMINES BY CATALYTIC HYDROGENATION OR REDUCTIVE ALKYLATION WITH DICHLOROBORANES.
-
1,2-aminoazides are easily prepared from 1,2-amino alcohols.Catalytic hydrogenation in the presence of palladium on charcoal or reductive alkylation with dichloroboranes afford with good yields unsymmetrically substituted vicinal diamines.
- Benalil, Aziza,Carboni, Bertrand,Vaultier, Michel
-
p. 8177 - 8194
(2007/10/02)
-
- Cephalosporin compound and pharmaceutical composition thereof
-
Cephalosporin compounds represented by the general formula (I): STR1 wherein R1 and R5 independently represent a hydrogen atom or a protective group for an amino group; R2 represents an alkyl group or a cycloalkyl group; R
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-
-
- Reductive Radical Decarboxylation of Amino-acids and Peptides
-
Radicals generated from N-protected α-amino-acids by photolysis of their N-hydroxypyridine-2-thione esters at room temperature are efficiently quenched by t-butyl thiol to give decarboxy-acids; comparable reactions have been carried out on the side chain carboxy groups of suitable protected aspartic and glutamic acids.
- Barton, Derek H. R.,Herve, Yolande,Potier, Pierre,Thierry, Josiane
-
p. 1298 - 1299
(2007/10/02)
-