- A convenient preparation of tetrahydrofuran-based diamines
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A convenient, three-step preparation of tetrahydrofuran-based diamines as combinatorial building blocks from 3,4-epoxytetrahydrofuran is described.
- Lai, Gaifa
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- SALT FORM AND CRYSTAL FORM OF COMPOUND AS FGFR4 INHIBITOR AND PREPARATION METHOD THEREOF
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The present invention provides a salt form, a crystal form, and a preparation method of a compound as an FGFR4 inhibitor and medical uses thereof.
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Paragraph 0141
(2021/04/02)
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- FGFR4 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
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Provided are a class of compounds as shown in formula (I) as FGFR4 inhibitors, and pharmaceutically acceptable salts thereof, preparation methods therefor and the use thereof in the preparation of drugs for treating FGFR4-related diseases.
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Paragraph 0377-0379
(2019/10/10)
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- SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE
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Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.
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Page/Page column 726
(2016/04/10)
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- SUBSTITUTED HETEROCYCLIC SULFONAMIDE COMPOUNDS USEFUL AS TRPA1 MODULATORS
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The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
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Paragraph 01202; 01203
(2015/04/28)
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- Catalytic asymmetric synthesis of thiols
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The synthesis of enantiopure thiols is of significant interest for industrial and academic applications. However, direct asymmetric approaches to free thiols have previously been unknown. Here we describe a novel organocascade that is catalyzed by a confined chiral phosphoric acid and furnishes O-protected β-hydroxythiols with excellent enantioselectivities. The method relies on an asymmetric thiocarboxylysis of meso-epoxides, followed by an intramolecular trans-esterification reaction. By varying the reaction conditions, the intermediate thioesters can also be obtained chemoselectively and enantioselectively.
- Monaco, Mattia Riccardo,Prvost, Sbastien,List, Benjamin
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supporting information
p. 16982 - 16985
(2015/02/18)
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- Organocatalytic asymmetric hydrolysis of epoxides
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The hydrolytic ring opening of epoxides is an important biosynthetic transformation and is also applied industrially. We report the first organocatalytic variant of this reaction, exploiting our recently discovered activation of carboxylic acids with chiral phosphoric acids via heterodimerization. The methodology mimics the enzymatic mechanism, which involves an enzyme-bound carboxylate nucleophile. A newly designed phosphoric acid catalyst displays high stereocontrol in the desymmetrization of meso-epoxides. The methodology shows wide generality with cyclic, acylic, aromatic, and aliphatic substrates. We also apply our method in the first highly enantioselective anti-dihydroxylation of simple olefins.
- Monaco, Mattia Riccardo,Prevost, Sebastien,List, Benjamin
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supporting information
p. 8142 - 8145
(2014/08/18)
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- Facile synthesis of chiral 1,2-chlorohydrins via the ring-opening of meso-epoxides catalyzed by chiral phosphine oxides
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The facile synthesis of chiral 1,2-chlorohydrins via the enantioselective ring-opening of meso-epoxides with silicon tetrachloride in the presence of a chiral phosphine oxide was accomplished. The chiral 1,2-chlorohydrins were also obtained from the corresponding cis-alkenes in one-pot without significant loss in the selectivity, thereby permitting easy access to the 1,2-chlorohydrins from cis-alkenes with good yields and enantioselectivities.
- Kotani, Shunsuke,Furusho, Haruka,Sugiura, Masaharu,Nakajima, Makoto
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p. 3075 - 3081
(2013/03/28)
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- SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE
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The present invention provides novel substituted cyclic compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 0173
(2013/09/26)
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- NOVEL TRIAZINE COMPOUNDS
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The present invention relates to novel triazine compounds of formula (1), methods of their preparation, pharmaceutical compositions containing these compounds and the use of these compounds to treat proliferative disorders such as tumors and cancers and also other conditions and disorders related to or associated with dysregulation of PI3 Kinases, PI3 Kinase pathway, mTOR and/ or the mTOR pathway.
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Page/Page column 66
(2012/08/08)
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- Kinase inhibitor compounds
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The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of kinase-mediated processes, and treatment of disease and disease symptoms, particularly those mediated by certain kinase enzymes.
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Page/Page column 23
(2009/04/24)
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- Enantioselective ring-opening of aziridines
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A process for the preparation of a nucleophilic addition product of an aziridine and a nucleophile, the process comprising treating the arizidine with the nucleophile in the presence of a biaryl phosphoric acid catalyst
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Page/Page column 15-16
(2009/02/11)
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- Intramolecular azide-alkyne [3 + 2] cycloaddition: Versatile route to new heterocyclic structural scaffolds
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Investigating the relatively unexplored intramolecular version of the azide-alkyne [3 + 2] cycloaddition, the present studies demonstrate the utility of the above reaction in the synthesis of a variety of as yet unreported heterocyclic structural scaffolds. The approach involved initial installation of strategic azide and alkyne moieties on a common structural framework, followed by their intramolecular cycloaddition studies. The pivotal azidoalkyne intermediates were efficiently accessed from a variety of easily available starting materials such as olefins, epoxides, amino acids, amino alcohols, ketones etc. The key reactions for incorporation of the azide functionality into the desired framework involved azidolysis of epoxides, displacement of hydroxy groups with azide nucleophiles, and diazo transfer on amine. Attachment of the desired alkyne functionalities was accomplished by either N-, or, O-alkylation with appropriate propargylic halides. The azidoalkynes thus prepared underwent smooth intramolecular cycloaddition, resulting in a variety of novel triazolooxazine and triazolopyrazine derivatives. Interestingly, unlike in the intermolecular version, metal catalysis was not necessary for the performance of the above cycloadditions. It is expected that the results from the present studies and its further extension will provide a potentially fertile pathway to a variety of unique chemical entities of structural and biological significance.
- Li, Rongti,Jansen, Daniel J.,Datta, Apurba
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experimental part
p. 1921 - 1930
(2009/06/28)
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- KINASE INHIBITOR COMPOUNDS
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The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of kinase-mediated processes, and treatment of disease and disease symptoms, particularly those mediated by certain kinase enzymes.
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Page/Page column 53
(2008/06/13)
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- Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications
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We previously reported a series of enantiopure cis-(1R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa Ki of 0.50 nM, PT EC2x of 2.1 μM in human plasma, bioavailability of 25% and t1/2of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented.
- Qiao, Jennifer X.,Wang, Tammy C.,Wang, Gren Z.,Cheney, Daniel L.,He, Kan,Rendina, Alan R.,Xin, Baomin,Luettgen, Joseph M.,Knabb, Robert M.,Wexler, Ruth R.,Lam, Patrick Y.S.
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p. 5041 - 5048
(2008/02/13)
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- Bronsted acid-catalyzed desymmetrization of meso-aziridines
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The enantioselective ring-opening of meso-aziridines with azide nucleophiles proceeded in the presence of a catalytic amount of a chiral phosphoric acid catalyst. The reaction affords the formation of the products in excellent yield and enantioselectivity. Preliminary mechanistic studies indicate that the active catalytic species is a chiral silane that is generated in situ. Copyright
- Rowland, Emily B.,Rowland, Gerald B.,Rivera-Otero, Edwin,Antilla, Jon C.
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p. 12084 - 12085
(2008/04/11)
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- Structure-activity studies of cyclic ketone inhibitors of the serine protease plasmin: Design, synthesis, and biological activity
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Three series of cyclic ketone inhibitors were synthesized and evaluated against the serine protease plasmin. Peptide inhibitors that incorporated 3-oxotetrahydrofuran and 3-oxotetrahydrothiophene 1,1-dioxide groups had the highest activities. Alkylamino substituents, which were designed to bind in the S1 subsite of plasmin, were attached to the inhibitors. Compounds 5c and 5g, which incorporated 6-aminohexyl substituents, were found to be optimal and demonstrated IC50 values in the low micromolar range. Incorporating conformationally constrained peptide segments into the inhibitors did not improve their activities.
- Xue, Fengtian,Seto, Christopher T.
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p. 8467 - 8487
(2008/02/05)
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- Process for halohydrin preparation
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A process for preparing a halohydrin of a water-miscible olefin comprising: reacting a water-miscible olefin in water with a compound of the formula (I) wherein R1 and R2 independently represent a branched or unbranched, substituted or unsubstituted, lower alkyl having from 1 to 5 carbons and X is a halogen, to thereby form the halohydrin of the water-miscible olefin.
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- 2-thiosubstituted carbapenems
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Carbapenem antibiotic compounds of the general formula: STR1 wherein the moiety STR2 is a 4, 5 or 6 membered mono, di- or tri- substituted oxygen or sulfur containing ring; wherein Z is oxygen, sulfur, sulfoxide and sulfone, pharmaceutical compositions thereof useful for the treatment of bacterial infections, processes for preparing the compounds and new intermediates useful in the process.
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- Derivatives of cyclic phenolic thioethers
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The present invention relates to derivatives of cyclic phenolic thioethers of the formula: STR1 and the pharmaceutically acceptable salts thereof, which are inhibitors or stimulators of superoxide generation, and which may also inhibit cyclooxygenase and/or 5-lipoxygenase, to pharmaceutical compositions containing one or more of these compounds in combination with a pharmaceutically-acceptable carrier, and to medical methods of treatment employing these compounds.
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- DERIVATIVES OF AROMATIC CYCLIC ALKYLETHERS
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The present invention provides compounds of the formula: and the pharmaceutically acceptable salts thereof, wherein: R1 and R2 are each alkyl; n is an integer of from 1 to 4; x is oxygen or -(CH2)m-; m is an integer of from 1 to 3; y is oxygen or sulfur; and p is an integer of from 1 to 4. These compounds are inhibitors of COX-I and/or COX-II, and are useful for the treatment of inflammation-associated disorders. The present invention also provides pharmaceutical compositions comprising a therapeutically-effective amount of a compound of Formula I in combination with a pharmaceutically-acceptable carrier, and a method for treating inflammation-associated disorders in an animal comprising administering a therapeutically-effective amount of a compound of Formula I to the animal
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- Nitrogenous macrocyclic ligands, polymetallic complexes and diagnostic and therapeutic composition
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The invention relates to ligands of formula STR1 in which B represents an STR2 W representing the STR3 group, in which groups X and Z represent a heterocycle. The invention also relates to the monometallic or polymetallic complexes formed by these ligands with metal ions chosen from lanthanide ions, transition metal ions. barium, bismuth, lead and the radioisotopes 99m Tc, 111 In, 90 Y, 64 Cu and 169 Yb, as well as the physiologically acceptable salts of these complexes. The salts of these complexes may be used as diagnostic or therapeutic agents in nuclear magnetic resonance imaging and X-ray radiology, as in-vivo chemical shift agents and in nuclear medicine. No figure
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- Regio- and Stereochemistry of the Acid Catalyzed and of a Highly Enantioselective Enzymatic Hydrolysis of Some Epoxytetrahydrofurans.
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3,4-Epoxytetrahydrofuran is hydrolyzed by rabbit liver microsomal epoxide hydrolase (MEH) with a high preference for the attack by water at the (S) epoxide carbon to give the (R,R)-diol with an e.e. of 96.5 +/- 0.3percent.In the acid catalyzed hydrolysis of trans-3,3a-epoxyoctahydrobenzofuran the oxirane ring is opened with inversion exclusively on the tertiary carbon atom to give the corresponding trans-diol, whereas hydrolysis of the cis isomer is less regioselective, the ratio of attack at the tertiary and secondary carbons being 81:19.The MEH catalyzed hydrolysis of the same two substrates occurs exclusively at their secondary carbons and with a very high enantioselectivity: only enantiomers of configuration (3S,3aR) of the cis- and trans-epoxide are substrates for the enzyme and give the corresponding (3R,3aR)-diols with at least 98percent e.e, the corresponding (3R,3aS)-epoxides being totally resistant to enzymatic hydrolysis.These results agree well with previously formulated rules on steric requirements of MEH substrates.Absolute configurations and optical purities of new chiral compounds were obtained by chiroptical, NMR and chiral chromatographic techniques.Conformations of the octahydrobenzofuran derivatives were derived from coupling constants and found to be in fairly good agreement with those deduced from molecular mechanics calculations.
- Barili, Pier Luigi,Berti, Giancarlo,Mastrorilli, Ettore
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p. 6263 - 6276
(2007/10/02)
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