- METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION
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Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.
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Paragraph 0570
(2021/11/20)
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- Preparation method and intermediate of benzodiazepine compound
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The invention discloses a preparation method of a benzodiazepine compound and an intermediate compound K. The compound K disclosed by the invention can be used for preparing the compound shown as theformula I in one step at high yield. The preparation met
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Paragraph 0057-0061
(2020/09/16)
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- Acceptor-Controlled Transfer Dehydration of Amides to Nitriles
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Palladium-catalyzed dehydration of primary amides to nitriles efficiently proceeds under mild, aqueous conditions via the use of dichloroacetonitrile as a water acceptor. A key to the design of this transfer dehydration catalysis is the identification of an efficient water acceptor, dichloroacetonitrile, that preferentially reacts with amides over other polar functional groups with the aid of the Pd catalyst and makes the desired scheme exergonic, thereby driving the dehydration.
- Okabe, Hiroyuki,Naraoka, Asuka,Isogawa, Takahiro,Oishi, Shunsuke,Naka, Hiroshi
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supporting information
p. 4767 - 4770
(2019/06/17)
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- COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF 1H-PYRAZOLO[4,3-B]PYRIDINES
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The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors together with a second compound useful in the treatment of a neurodegenerative disorder and their combined use as a medicament, in particular for the treatment of neurodegenerative and/or cognitive disorders.
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Page/Page column 106; 107
(2019/07/19)
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- 1H-PYRAZOLO[4,3-B]PYRIDINES AS PDE1 INHIBITORS
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The present invention provides 1H-pyrazolo[4,3-b]pyridines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
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Paragraph 0500-0501
(2019/07/10)
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- COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF 1H-PYRAZOLO[4,3-B]PYRIDINES
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The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors together with a second compound which compound is useful in the treatment of a psychiatric disorder and their combined use as a medicament, in particular for the treatment of psychiatric and/or cognitive disorders.
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Page/Page column 103-104
(2019/07/19)
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- PYRAZOLO[3,4-b]PYRIDINES AND IMIDAZO[1,5-b]PYRIDAZINES AS PDE1 INHIBITORS
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The present invention provides compounds of formula (I) that are PDE1 enzyme inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders. The present invention also provides pharmaceutical compositions comprising compounds of the invention and methods of treating disorders using the compounds of the invention.
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Paragraph 0376; 0377
(2018/07/15)
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- HETEROCYCLIC COMPOUNDS AND USE THEREOF
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Heterocyclic compounds of Formula (I) shown herein. Also disclosed is a pharmaceutical composition containing one of the heterocyclic compounds. Further disclosed are methods of using one of the heterocyclic compounds for mobilizing hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation, and for treating tissue injury, cancer, inflammatory disease, and autoimmune disease.
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Page/Page column 27; 28
(2018/08/03)
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- 1H-PYRAZOLO[4,3-B]PYRIDINES AS PDE1 INHIBITORS
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The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
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Page/Page column 98
(2018/09/25)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS AS TROPOMYOSIN RECEPTOR KINASE A (TRKA) INHIBITORS
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The present application relates to a series of substituted pyrazolo[1,5-a]pyridine compounds, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.
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Paragraph 1085 - 1087
(2015/02/05)
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- One-pot synthesis of orthogonally protected dipeptide selenazoles employing Nα-amino selenocarboxamides and α-bromomethyl ketones
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A simple and efficient protocol for the synthesis of selenazole containing dipeptidomimetics using Nα-amino selenocarboxamides and α-bromomethyl ketones is described. All the compounds made were isolated in good yields and fully characterized.
- Madhu, Chilakapati,Panguluri, Nageswara Rao,Narendra,Panduranga,Sureshbabu, Vommina V.
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p. 6831 - 6835
(2015/01/09)
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- 2-Substituted 4,5-dihydrothiazole-4-carboxylic acids are novel inhibitors of metallo-β-lactamases
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Bacterial resistance to β-lactam antibiotics caused by class B metallo-β-lactamases (MBL), especially for certain hospital-acquired, Gram-negative pathogens, poses a significant threat to public health. We report several 2-substituted 4,5-dihydrothiazole-4-carboxylic acids to be novel MBL inhibitors. Structure activity relationship (SAR) and molecular modeling studies were performed and implications for further inhibitor design are discussed.
- Chen, Pinhong,Horton, Lori B.,Mikulski, Rose L.,Deng, Lisheng,Sundriyal, Sandeep,Palzkill, Timothy,Song, Yongcheng
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supporting information
p. 6229 - 6232
(2012/10/29)
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- Fibrinogen receptor antagonists and their use
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This invention relates to novel fused bicyclic compounds of the general formula (I): wherein the symbols are defined herein, to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and to methods of using the compounds, alone or in combination with other therapeutic agents. The compounds are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, and are therefore useful for the inhibition of platelet aggregation, and for the treatment of thrombotic diseases and other diseases.
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Page/Page column 105
(2010/08/04)
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- Synthesis of tricyclic fused 3-aminopyridines through intramolecular Coi-catalyzed [2+2+2] cycloaddition between ynamides, nitriles, and alkynes
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The first [2+2+2] cocyclizations between ynamides, nitriles, and alkynes are reported. They open a new access to unprecedented nitrogen-containing heterocycles of type 2-trimethylsilyl-3-aminopyridines. Such frameworks, which can be found in various compo
- Garcia, Pierre,Moulin, Solenne,Mielo, Yves,Leboeuf, David,Gandon, Vincent,Aubert, Corinne,Malacria, Max
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experimental part
p. 2129 - 2139
(2009/09/06)
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- Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors
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Human immunodeficiency virus type-1 (HIV-1) integrase, one of the three constitutive viral enzymes required for replication, is a rational target for chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clinical setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these molecules were made in order to examine effects on HIV-integrase inhibitory potencies. One of the most interesting compounds for this series is 2-[1-(dimethylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine- 4-carboxamide 38, with a CIC95 of 78 nM in the cell-based assay in the presence of serum proteins. The compound has favorable pharmacokinetic properties in preclinical species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clinically useful antiviral agent.
- Pace, Paola,Di Francesco, M. Emilia,Gardelli, Cristina,Harper, Steven,Muraglia, Ester,Nizi, Emanuela,Orvieto, Federica,Petrocchi, Alessia,Poma, Marco,Rowley, Michael,Scarpelli, Rita,Laufer, Ralph,Paz, Odalys Gonzalez,Monteagudo, Edith,Bonelli, Fabio,Hazuda, Daria,Stillmock, Kara A.,Summa, Vincenzo
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p. 2225 - 2239
(2007/10/03)
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- 4,5-Dihydroxypyrimidine carboxamides and N-alkyl-5-hydroxypyrimidinone carboxamides are potent, selective HIV integrase inhibitors with good pharmacokinetic profiles in preclinical species
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The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochemical properties, pharmacokinetic profiles, and potency led to the identification of 13 in the dihydroxypyrimidine series and 18 in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclinical species.
- Summa, Vincenzo,Petrocchi, Alessia,Matassa, Victor G.,Gardelli, Cristina,Muraglia, Ester,Rowley, Michael,Paz, Odalys Gonzalez,Laufer, Ralph,Monteagudo, Edith,Pace, Paola
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p. 6646 - 6649
(2007/10/03)
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- FIBRINOGEN RECEPTOR ANTAGONISTS AND THEIR USE
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This invention relates to novel fused bicyclic compounds of the general formula (I): wherein the symbols are defined herein, to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and to methods of using the compounds, alone or in combination with other therapeutic agents. The compounds are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, and are therefore useful for the inhibition of platelet aggregation, and for the treatment of thrombotic diseases and other diseases.
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Page/Page column 120
(2010/02/11)
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- Aryl substituted bicyclic amines as selective dopamine D3 ligands
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Compounds and their pharmaceutically acceptable salts suitable for treating central nervous system disorders associated with the dopamine D3 receptor activity of structural Formula I:
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- Process for producing 1-substituted-hydantoins
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The subject is to provides a process for producing 1-substituted-hydantoins of Formula I: wherein R1represents a hydrocarbon group which may be substituted and others,characterized by reacting N-substituted-N-alkoxycarbonylamino-acetonitrile of Formula II: wherein R2represents an alkyl group and others,with an alkali metal hydroxides or the like and then treating with an acid.
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- Inverse Electron Demand Diels-Alder Reactions of Indole IV. A New Route to β-Carbolines
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β-Carbolines have been prepared by the intramolecular cycloaddition of indole with 1,2,4-triazines tethered from C3 with the indolyl nitrogen using a thiourea linkage.Subsequent to the cycloaddition, reductive cleavage of the thiourea subunit provides the β-carboline.
- Fan, Wen-Hong,Parikh, Mamta,Snyder, John K.
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p. 6591 - 6594
(2007/10/02)
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- Benzotriazole-assisted Synthesis of α-Acylaminonitriles and a Conceptually Novel Method for Peptide Elongation
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A general method for the synthesis of α-acylamino nitriles is reported.Initially, the adducts resulting from Mannich-type condensation of benzotriazole with an aldehyde and an amide are prepared.These undergo elimination of benzotriazole with cyanide to g
- Katritzky, Alan R.,Urogdi, Laszlo
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p. 1853 - 1857
(2007/10/02)
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- Amino Acids and Peptides; 59. Synthesis of Biologically Active Cyclopeptides; 9. Synthesis of 16 Isomers of Dolastatin 3; I. Synthesis of the 2-(1-aminoalkyl)-thiazole-4-carboxylic Acids
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The synthesis of the optically active Dolastatin 3 building block 2-(1-amino-3-cyanopropyl)-thiazole-4-carboxylic acid is described as a prerequisite for the total synthesis of dolastatin isomers.
- Schmidt, Ulrich,Utz, Roland,Lieberknecht, Albrecht,Griesser, Helmut,Potzolli, Bernd,et al.
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p. 233 - 236
(2007/10/02)
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- Studies on Amino Acids and Peptides. Part 6. Methods for Introducing Thioamide Bonds into the Peptide Backbone: Synthesis of the Four Monothio Analogues of Leucine Enkephalin
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A methodology for preparing peptide analogues in which a thioamide bond replaces the normal amide bond is described.Thus, the synthesis of the three leucine enkephalin analogues 4>-, 2>-, and 1>-leucine enke
- Clausen, Kim,Thorsen, Michael,Lawesson, Sven-Olov,Spatola, Arno F.
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p. 785 - 798
(2007/10/02)
-
- Resonance Raman spectroscopic evidence for an intramolecular interaction involving th amide and dithioester groups of N-acyl glycine ethyl dithioesters
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The synthesis and resonance Raman spectra of several new N-acyl glycine etyl dithioesters RC(=O)NHCH2C(=S)SR are reported.The resonance Raman spectra of these compounds contain at least two peaks in the "C=S stretching region" between 1050 and 1200 cmsup
- Storer, A. C.,Ozaki, Y.,Carey, P. R.
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p. 199 - 209
(2007/10/02)
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- Purines, Pyrimidines, and Imidazoles. Part 54. Interconversion of Some Intermediates in the de novo Biosynthesis of Purine Nucleotides
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Ethyl and benzyl 5-amino-1-(2-pyridyl)imidazole-4-carboxylates, obtained from ethyl or benzyl α-amino-α-cyanoacetate, respectively, and ethyl formimidate hydrochloride followed by 2-aminopyridine, were converted into 5-amino-1-(2-pyridyl)imidazole-4-carboxylic acid which was decarboxylated in situ to 5-amino-1-(2-pyridyl)imidazole.Reaction of 2-N-formylamino-N-(2-pyridyl)acetamide with ammonia and ammonium chloride gave 5-aminoimidazole and a similar reaction with the nucleotide 2-N-formylglicineamide ribotide similarly gave evidence for aminoimidazole formation. 4-Cyano-5- imidazolone, prepared by reaction of 2-cyano-N-formylacetamide with nitrous acid and reduction of the hydroxyimino derivative so produced, with ammonia and ammonium sulphite at 100 deg C, gave 5-aminoimidazole-4-carboxamide.Implications of the reactions involved are discussed.
- Cusack, Noel J.,Shaw, Gordon,Logemann, Fatma I.
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p. 2316 - 2321
(2007/10/02)
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