- BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
-
The present invention relates to compounds useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
- -
-
Paragraph 0880; 0881; 0882
(2020/05/21)
-
- As Aurora kinase inhibitors of the substituted quinazoline derivatives
-
The invention relates to a substituted quinazoline derivative as an aurora kinase inhibitor, which is shown as structural formula (I) or (Ia), tautomers, hydrates, solvates or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the tautomers, hydrates, solvates and pharmaceutically acceptable salts as drug active ingredients, and application of the compounds and the pharmaceutical compositions in preparation of medicines for protection, treatment, curing or alleviation of proliferative diseases of patients.
- -
-
Paragraph 0291; 0294-0296
(2019/04/04)
-
- As Aurora kinase inhibitor derivatives
-
The present invention relates to a substituted pyrazole derivative used for inhibiting Aurora kinase and represented by formula (I) or formula (Ia), or stereo isomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts or prodrugs thereof, a medicinal composition containing the above compounds as active ingredients, and a use of the compounds and the medicinal composition in preparation of medicines for protecting, processing, treating or mitigating proliferative diseases of patients.
- -
-
Paragraph 0612; 0615; 0616
(2019/06/27)
-
- Pyrrolidine ring puckering and prolyl amide bond configurations of 2-methyl-allo-hydroxyproline-based dipeptides
-
An expeditious method for the synthesis of homo and heterochiral dipeptides containing l-alanine and d/l 2-methyl allo-hydroxyl prolines was developed using direct aminolysis of bicyclic lactones derived from d/l alanine. The impact of C-2 methylation and its spatial orientation on the pyrrolidine ring puckering and prolyl amide bond configuration was ascertained by solution NMR studies. The present studies reveal that C-2 methylation causes the prolyl amide bond to exist exclusively in the trans geometry in both homo- and heterochiral dipeptides. However, the spatial orientation of the C-2 methyl group and its i + 2 position in appropriately capped model dipeptides may nucleate into a turn like structure.
- Tiwari, Vinay Shankar,Singh, Gajendra,Gurudayal,Ampapathi, Ravi Sankar,Haq, Wahajul
-
supporting information
p. 4460 - 4464
(2019/05/17)
-
- CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
-
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
- -
-
Paragraph 00576-00578
(2019/06/11)
-
- 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 0022-0025
(2019/10/15)
-
- Substituted pyridine compound and its method and use thereof
-
The invention relates to a novel substitutive pyridine compound, and a pharmaceutically acceptable salt and a pharmaceutical preparation of the substitutive pyridine compound for regulating the activity of protein kinases and regulating signal responses between cells or in the cells. Meanwhile, the invention further relates to a pharmaceutical composition containing the compound provided by the invention, and a method for treating high proliferative diseases of mammals, especially human with the pharmaceutical composition.
- -
-
Paragraph 0458; 0459
(2018/06/21)
-
- SPIRO-LACTAM AND BIS-SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Page/Page column 63
(2018/03/28)
-
- 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
(2018/05/27)
-
- N-methyl-D-aspartate receptor modulators and methods of making and using same
-
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Page/Page column 60; 62
(2018/06/25)
-
- INDOLE DERIVATIVES AS EFFLUX PUMP INHIBITORS
-
Disclosed herein are compounds of formula (I): and salts thereof. Also disclosed are compositions comprising compounds of formula I and compounds of formula I for use in treating or preventing bacterial infections.
- -
-
Page/Page column 85-86
(2018/09/28)
-
- Construction of Challenging Proline-Proline Junctions via Diselenide-Selenoester Ligation Chemistry
-
Polyproline sequences are highly abundant in prokaryotic and eukaryotic proteins, where they serve as key components of secondary structure. To date, construction of the proline-proline motif has not been possible owing to steric congestion at the ligatio
- Sayers, Jessica,Karpati, Phillip M. T.,Mitchell, Nicholas J.,Goldys, Anna M.,Kwong, Stephen M.,Firth, Neville,Chan, Bun,Payne, Richard J.
-
supporting information
p. 13327 - 13334
(2018/10/20)
-
- Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains
-
As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki= 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki= 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki= 8.45 μM), which was the same as positive control Gossypol (Ki= 7.54 μM).
- Wan, Yichao,Liu, Tingting,Li, Xiaoxian,Chen, Chen,Fang, Hao
-
p. 138 - 152
(2016/12/22)
-
- PYRROLOTRIAZINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to pyrrolotriazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 48
(2016/09/26)
-
- PYRAZOLOPYRIMIDINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to pyrazolopyrimidine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 73
(2016/09/26)
-
- Production of deriv. hydroxyproline
-
PROBLEM TO BE SOLVED: To provide a production method which inexpensively produces a hydroxyproline derivative useful as a raw material of a medicine and an agricultural chemical by using an inexpensive raw material at high yield, and is suitable for industrial production. SOLUTION: The hydroxyproline derivative expressed by a general formula (2) is produced by N-acylating hydroxyproline in the co-existence of at least one of bases selected from an alkali metal carbonate, an alkali earth metal carbonate, an alkali metal bicarbonate and an alkali earth metal bicarbonate. In the formula, R1denotes 1C-6C alkyl, aryl or aralkyl, and R2denotes 1C-6C alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl or aralkyloxycarbonyl. COPYRIGHT: (C)2012,JPOandINPIT
- -
-
Paragraph 0042
(2016/10/20)
-
- Production of cis-4-hydroxyproline
-
PROBLEM TO BE SOLVED: To produce cis-4-hydroxyproline useful as a raw material of medicines and agrochemicals by an industrially suitable method.SOLUTION: The method for producing cis-4-hydroxyproline includes: hydrolyzing a hydroxyproline derivative represented by formula (1), wherein Rdenotes a 1-6C alkylcarbonyl group, an arylcarbonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, or an aralkyloxycarbonyl group, in the presence of a hydrochloric acid catalyst; neutralizing the resultant with an organic base; and thereafter diluting the resultant with an alcohol.
- -
-
Paragraph 0051
(2018/11/24)
-
- Synthesis of (1R,4R)-2,5-diazabicyclo[2.2.1]heptane derivatives by an epimerization-lactamization cascade reaction
-
An epimerization-lactamization cascade of functionalized (2S,4R)-4-aminoproline methyl esters is developed and applied in synthesizing (1R,4R)-2,5-diazabicyclo[2.2.1]heptane (DBH) derivatives. (2S,4R)-4-Aminoproline methyl esters are likely to undergo 2-epimerization under basic conditions, followed by an intramolecular aminolysis of the (2R)-epimer to form the bridged lactam intermediates. Key factors identified for this cascade reaction include the electron-withdrawal N-protective group in the substrates and a strong base as the promoter.
- Cui, Benqiang,Yu, Jie,Yu, Fu-Chao,Li, Ya-Min,Chang, Kwen-Jen,Shen, Yuehai
-
p. 10386 - 10392
(2015/01/30)
-
- 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.
-
p. 3171 - 3181
(2015/03/18)
-
- HYDROXYPROLINE DERIVATIVE
-
PROBLEM TO BE SOLVED: To provide hydroxyproline derivatives useful as catalysts for e.g. Michael addition reactions and their salts. SOLUTION: Hydroxyproline derivatives having a relative configuration of formula (I) and their salts are provided. In formu
- -
-
Paragraph 0172; 0180
(2017/01/02)
-
- PYRAZOLINE DERIVATIVES AND THEIR USE AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
-
The invention relates to a compound of formula (I) in free form or in pharmaceutically acceptable salt form (I), in which the substituents are as defined in the specification; to compounds of formula (I) for use as androgen receptor modulators. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
- -
-
Paragraph 0443; 0444; 0445; 0446; 0459; 0460
(2014/11/13)
-
- Enantioselective Michael addition of cyclic ketones to nitroolefins catalyzed by a novel fluorine-insertion organocatalyst
-
A novel fluorine-insertion organocatalyst, which was designed based on the fluorine-ammonium ion gauche effect, was synthesized and used successfully to catalyze the asymmetric Michael addition of cyclic ketones to nitroolefins. High yields and excellent diastereo- and enantioselectivities were achieved under mild conditions. A possible stereochemical model is also proposed.
- Wang, Yanan,Jiang, Min,Liu, Jin-Tao
-
p. 212 - 218
(2014/03/21)
-
- Enantioselective synthesis and physicochemical properties of libraries of 3-amino- and 3-amidofluoropiperidines
-
The enantioselective syntheses of 3-amino-5-fluoropiperidines and 3-amino-5,5-difluoropiperidines were developed using the ring enlargement of prolinols to access libraries of 3-amino- and 3-amidofluoropiperidines. The study of the physicochemical properties revealed that fluorine atom(s) decrease(s) the pKa and modulate(s) the lipophilicity of 3-aminopiperidines. The relative stereochemistry of the fluorine atoms with the amino groups at C3 on the piperidine core has a small effect on the pK a due to conformationnal modifications induced by fluorine atom(s). In the protonated forms, the C-F bond is in an axial position due to a dipole-dipole interaction between the N-H+ and C-F bonds. Predictions of the physicochemical properties using common software appeared to be limited to determine correct values of pKa and/or differences of pK a between cis- and trans-3-amino-5-fluoropiperidines.
- Orliac, Aurelie,Routier, Julie,Burgat Charvillon, Fabienne,Sauer, Wolfgang H. B.,Bombrun, Agnes,Kulkarni, Santosh S.,Gomez Pardo, Domingo,Cossy, Janine
-
supporting information
p. 3813 - 3824
(2014/04/03)
-
- Substituted Imidazopyridines as HDM2 Inhibitors
-
The present invention provides substituted imidazopyridines as described herein or a pharmaceutically acceptable salt or solvate thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.
- -
-
Paragraph 0765
(2014/07/08)
-
- PYRAZOLINE DERIVATIVES AND THEIR USE AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
-
The invention relates to a compound of formula (I) in free form or in pharmaceutically acceptable salt form (I), in which the substituents are as defined in the specification; to compounds of formula (I) for use as androgen receptor modulators. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition
- -
-
Page/Page column 50
(2013/03/26)
-
- 1,3,4-OXADIAZOLE AND 1,3,4-THIADIAZOLE BETA-LACTAMASE INHIBITORS
-
β-Lactamase inhibitor compounds (BLIs) are disclosed, including compounds that have activity against class A, class C or class D β-lactamases. Methods of manufacturing the BLIs, and uses of the compounds in the preparation of pharmaceutical compositions and antibacterial applications are also disclosed.
- -
-
Page/Page column 132; 133
(2013/10/21)
-
- A novel method to access chiral nonnatural 2,4-disubstituted pyrrolidines from aldehydes and nitroolefins only with an α-substituent
-
A series of α-substituted nitroolefins were employed in organocatalytic asymmetric Michael reactions with aldehydes. γ-Nitro carbonyl products were achieved in good yields (up to 86%) with good stereoselectivities (up to 96% ee and 24 : 1 dr). Reduction of the nitro group followed by intramolecular reductive amination successfully afforded various novel optically active 2,4-disubstituted pyrrolidine compounds.
- Zheng, Bo,Wang, Hui,Han, Yong,Liu, Changlu,Peng, Yungui
-
supporting information
p. 4561 - 4563
(2013/06/04)
-
- 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 71
(2013/07/19)
-
- C3′-endo-puckered pyrrolidine containing PNA has favorable geometry for RNA binding: Novel ethano locked PNA (ethano-PNA)
-
A novel peptide nucleic acid (PNA) analogue is designed with a constraint in the aminoethyl segment of the aegPNA backbone so that the dihedral angle β is restricted within 60-80, compatible to form PNA:RNA duplexes. The designed monomer is further functionalized with positively charged amino-/guanidino-groups. The appropriately protected monomers were synthesized and incorporated into aegPNA oligomers at predetermined positions and their binding abilities with cDNA and RNA were investigated. A single incorporation of the modified PNA monomer into a 12-mer PNA sequence resulted in stronger binding with complementary RNA over cDNA. No significant changes in the CD signatures of the derived duplexes of modified PNA with complementary RNA were observed.
- Banerjee, Anjan,Kumar, Vaijayanti A.
-
p. 4092 - 4101
(2013/07/27)
-
- 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 0238; 0239
(2013/11/06)
-
- L-Proline derived nitrogenous steroidal systems: An asymmetric approach to 14-azasteroids
-
An efficient chiral pool approach using l-proline to access 14-azasteroids under mild reaction conditions has been described. The key step involves the intramolecular SN2′ cyclization reaction for the construction of critical C-ring in the nitrogen impregnated steroidal architectures bearing unsaturation at Δ9(11) position. In the endeavour to synthesize some new congeners, the remote electronic impact of the electron donating groups in A ring and heteroatoms like oxygen in B ring, on the propensity of C-ring cyclization was also observed.
- Singh, Ritesh,Panda, Gautam
-
p. 19533 - 19544
(2013/10/22)
-
- Structure-reactivity studies of simple 4-hydroxyprolinamide organocatalysts in the asymmetric Michael addition reaction of aldehydes to nitroolefins
-
A series of simple 4-hydroxyprolinamides was synthesised and they were found to act as organocatalysts for the asymmetric conjugate addition of aldehydes to nitroolefins in excellent yields (98%), with complete diastereoselectivity (99:1, syn:anti) and enantioselectivity (98% ee for syn). Furthermore, the use of low catalyst loadings (5mol%) and a low aldehyde molar excess (1.5equivalents) were achieved. Copyright
- Watts, John,Luu, Lien,McKee, Vickie,Carey, Ed,Kelleher, Fintan
-
supporting information; experimental part
p. 1035 - 1042
(2012/05/20)
-
- 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
-
experimental part
p. 5286 - 5296
(2012/08/27)
-
- Asymmetric Michael addition induced by the anion of an imidazolium salt
-
We describe the application of a chiral catalytic imidazolium salt derived from trans-L-hydroxyproline, the anion being the catalytic entity, as a catalyst for the asymmetric Michael addition. We report the first example of a catalytic Michael addition us
- Gauchot, Vincent,Gravel, Julien,Schmitzer, Andreea R.
-
p. 6280 - 6284,5
(2020/09/16)
-
- Access to optically active 3-aminopiperidines by ring expansion of prolinols: Thermodynamic versus kinetic control
-
3-Aminopiperidines are of great interest because they can possess a wide range of biological activity depending on the nitrogen substituents. Different approaches their synthesis are presented and the most efficient is a ring expansion of prolinols induce
- Cochi, Anne,Pardo, Domingo Gomez,Cossy, Janine
-
experimental part
p. 2023 - 2040
(2012/05/20)
-
- Synthesis of chiral pyrrolidine isostere inserted into pyrrole polyamide skeleton
-
An efficient and general route towards the synthesis of a series of chiral pyrrolidine pyrrole polyamide distamycin analogues starting from (L)-hydroxyproline is described. The binding abilities of these chiral pyrrolidine containing molecules to calf thymus DNA were evaluated by duplex DNA melting temperature analysis. The results revealed that both the chirality at the pyrrolidine ring and the site of incorporation plays an important role for binding at the duplex DNA.
- Lin, Chun-Yu,Yang, Ya-Ting,Ong, Chi Wi
-
scheme or table
p. 436 - 442
(2012/07/27)
-
- The synthesis of piperidine nucleoside analogs - A comparison of several methods to access the introduction of nucleobases
-
This work deals with the synthesis of piperidine and hydroxypiperidine analogs of nucleosides. Starting from commercially available 3-hydroxypiperidine, proline or 4-hydroxyproline, a series of piperidine derivatives of both purine and pyrimidine nucleobases was prepared. Various methods of nucleobase attachment were evaluated. The prepared compounds were tested for cytostatic, antibacterial, and antiviral properties but no significant activity was found.
- Kova?ková, Soňa,Dra?ínsky, Martin,Rejman, Dominik
-
experimental part
p. 1485 - 1500
(2011/04/15)
-
- 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)
-
- A highly efficient flow reactor process for the synthesis of N-Boc-3,4-dehydro-l-proline methyl ester
-
The multi-step preparation of N-Boc-3,4-dehydro-l-proline methyl ester using a modular flow reactor is reported. The use of immobilised reagents and scavengers in pre-packed glass tubes allows us to obtain the pure product in 87% overall yield, 97% purity, and >98% enantiomeric excess without any additional purification step. Our flow-based protocol enables the rapid multi-gram synthesis (about 9 g/12 h) of the desired product.
- Tamborini, Lucia,Conti, Paola,Pinto, Andrea,Micheli, Carlo De
-
experimental part
p. 222 - 225
(2010/05/02)
-
- 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 57
(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
-
scheme or table
p. 1557 - 1572
(2009/08/15)
-
- 4-Trifluoromethanesulfonamidyl prolinol tert-butyldiphenylsilyl ether as a highly efficient bifunctional organocatalyst for Michael addition of ketones and aldehydes to nitroolefins
-
4-Trifluoromethanesulfonamidyl prolinol tert-butyldiphenylsilyl ether bifunctional organocatalyst 3a is a highly efficient catalyst for the asymmetric Michael addition reactions of ketones and aldehydes to nitrostyrenes, leading to syn-selective adducts with excellent yields (>99%), high diastereoselectivities (up to 99:1 dr) and excellent enantioselectivities (up to 99% ee). Control experiments suggested that the trans-configuration relationship between the bulky group (-CH2OTBDPS) and the sulfonamido group at the 4-position of the pyrrolidine ring was important to achieve high yield and stereoselectivity.
- Wang, Chao,Yu, Chun,Liu, Changlu,Peng, Yungui
-
supporting information; experimental part
p. 2363 - 2366
(2009/08/17)
-
- Stereoselective synthesis and biological evaluations of novel 3′-deoxy-4′-azaribonucleosides as inhibitors of hepatitis C virus RNA replication
-
3′-Deoxy-4′-azaribonucleosides (15a-d) were synthesized starting from the commercially available (4R)-trans-4-hydroxy-L-proline 7. From biological evaluations, 15b and 15d emerged as potent inhibitors of HCV replication on a replicon assay. These findings demonstrate that synthesized pyrrolidine nucleosides represent a new template for antiviral or other biological studies and could be considered for novel combination therapy against HCV infection using nucleoside inhibitors and non-nucleoside inhibitors of HCV NS5B.
- Chiacchio, Ugo,Borrello, Luisa,Crispino, Lia,Rescifina, Antonio,Merino, Pedro,Macchi, Beatrice,Balestrieri, Emanuela,Mastino, Antonio,Piperno, Anna,Romeo, Giovanni
-
scheme or table
p. 4054 - 4057
(2009/12/24)
-
- HCV PROTEASE INHIBITORS
-
This invention relates to the compounds of formula (I) shown below. Each variable in formula (I) is defined in the specification. These compounds can be used to treat hepatitis C virus infection.
- -
-
Page/Page column 20
(2008/12/04)
-
- Development of a kilogram-scale synthesis of cis-LC15-0133 tartrate, a potent dipeptidyl peptidase IV inhibitor
-
(45)-N-Boc-4-fluoro-L-proline methyl ester (4) was prepared from the following sequence of reactions: esterification of trans-4-hydroxy-L-proline (2), Boc protection, and fluorination by DAST. Reaction of 4 with lithiated oxadiazole provided oxadiazolyl ketone 7. Deprotection of the Boc group of 7 and subsequent coupling with bromoacetyl bromide gave bromide 9. Coupling reaction of 9 with excess oxazolidine 16 provided coupled product 17. Unexpectedly, the stereogenic center of 17 was completely epimerized to a virtually 1:1 mixture of cis- and trans-17 at this stage. After the deprotection of the N,O-methylene acetal group of 17 using aqueous ammonium chloride, crystallization induced dynamic resolution (CIDR) of cis- and Awns-mixture of LC15-0133 (1) in the course of tartrate salt formation provided cis-LC15-0133 (1a) tartrate salt in 83% yield (>98% de).
- Kim, Bong Chan,Kim, Kyu-Young,Lee, Hee Bong,Shin, Hyunik
-
p. 626 - 631
(2013/01/03)
-
- TRANS-3,5-DISUBSTITUTEDPYRROLIDINE: ORGANOCATALYST FOR anti-MANNICH REACTIONS
-
A compound of Formula I is disclosed, in which R is a substituent containing a hydrogen bond-forming atom within three atoms from the ring carbon to which the substituent is bonded; X is CH2, O, S or NR1, wherein R1 is a hydrocarbyl group or an amino-protecting group having one to about 18 carbon atoms; R2 is hydrido or a hydrocarbyl group containing one to about twelve carbon atoms; and R3 is hydrido or methyl, but both R2 and R3 are not hydrido when X is CH2 A molecule of Formula I and those in which R2 and R3 can both be hydrido (Formula X) functions as a catalyst in a Mannich reaction to asymmetrically form β-aminoaldehyde or β-aminoketone diastereomeric products having two chiral centers on adjacent carbon atoms and in which the anti-diastereomers are in excess over the syn-diastereomers. Methods for carrying out those syntheses are also disclosed.
- -
-
Page/Page column 21; 22
(2010/11/27)
-
- Solvent-free organocatalytic asymmetric conjugate addition of thiols to α,β-unsaturated aldehydes
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A highly enantioselective asymmetric conjugate addition of thiols to α,β-unsaturated aldehydes has been achieved catalyzed by newly designed organocatalyst without solvent. Copyright
- Ishino, Takeru,Oriyama, Takeshi
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p. 550 - 551
(2008/02/10)
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- Highly enantioselective synthesis of β-amino alcohols: A catalytic version
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(Chemical Equation Presented) Highly enantioselective rearrangement of β-amino alcohols was realized by using a catalytic amount of trifluoroacetic anhydride.
- Metro, Thomas-Xavier,Pardo, Domingo Gomez,Cossy, Janine
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p. 6556 - 6561
(2008/02/10)
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- Cytotoxic agents comprising new tomaymycin derivatives
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The present invention is related to new tomaymycin derivatives of formula (I), their process of preparation and their therapeutic uses.
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Page/Page column 41
(2008/06/13)
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- ANTIVIRAL COMPOUNDS
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The invention is related to phosphorus substituted anti-viral inhibitory 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.
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Page/Page column 319-320
(2008/06/13)
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