- PYRAZOLE AND IMIDAZOLE DERIVATIVES, COMPOSITIONS AND METHODS AS OREXIN ANTAGONISTS
-
The present invention is directed to substituted Pyrazole and Imidazole derivatives of compounds that are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which
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-
Page/Page column 35; 41
(2020/12/29)
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- IMIDAZOLO DERIVATIVES, COMPOSITIONS AND METHODS AS OREXIN ANTAGONISTS
-
This disclosure is directed to substituted Imidazolo[2,1-b]oxazole, lmidazolo[2,1-b]thiazole, Imidazolo[2,1-b]oxadiazole, lmidazolo[2,1-b]oxadiathiazole derivatives of compounds that are antagonists of orexin receptors, and which are useful in the treatme
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-
Page/Page column 31; 32
(2020/12/29)
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- Chiral phosphine nitrogen phosphine ligand and chiral metal organic coordination complex and application
-
The invention discloses a chiral phosphine nitrogen phosphine ligand and chiral metal organic coordination complex and application. The chiral tridentate phosphine nitrogen phosphine ligand is shown as a formula (I), and the chiral metal organic coordination complex is shown as a formula (II), wherein the chiral metal organic coordination complex shown as the formula (II) is used as a homogeneouscatalyst to be applied to preparation of phenylalanine derivatives with high optical activity. The novel chiral nitrogen-phosphine ligand synthesized by taking cheap amino acid as a chiral source is applied to asymmetric hydrogenation reaction, and a chiral product with relatively high yield can be obtained with relatively low catalytic dosage, relatively short reaction time and relatively mild reaction conditions.
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-
Paragraph 0063-0065
(2020/07/02)
-
- Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors
-
ABTRACT: In this paper, a new series of isatin-sulphonamide based derivatives were designed, synthesised and evaluated as caspase inhibitors. The compounds containing 1-(pyrrolidinyl)sulphonyl and 2-(phenoxymethyl)pyrrolidin-1-yl)sulphonyl substitution at C5 position of isatin core exhibited better results compared to unsubstituted derivatives. According to the results of caspase inhibitory activity, compound 20d showed moderate inhibitory activity against caspase-3 and ?7 in?vitro compared to Ac-DEVD-CHO (IC50 = 0.016 ± 0.002 μM). Among the studied compounds, some active inhibitors with IC50s in the range of 2.33–116.91 μM were identified. The activity of compound 20d was rationalised by the molecular modelling studies exhibiting the additional van der Waals interaction of N-phenylacetamide substitution along with efficacious T-shaped π-π and pi-cation interactions. The introduction of compound 20d with good caspase inhibitory activity will help researchers to find more potent agents.
- Firoozpour, Loghman,Gao, Lixin,Moghimi, Setareh,Pasalar, Parvin,Davoodi, Jamshid,Wang, Ming-Wei,Rezaei, Zahra,Dadgar, Armin,Yahyavi, Hoda,Amanlou, Massoud,Foroumadi, Alireza
-
p. 1674 - 1684
(2020/09/02)
-
- Synthesis and Stereochemical Assignment of Conioidine A: DNA- And HSA-Binding Studies of the Four Diastereomers
-
Conioidine A (1), isolated in 1993 with unknown relative and absolute configuration, was suggested to be a DNA-binding compound by an indirect technique. Four stereoisomers of conioidine A have been synthesized from d- and l-proline, and the natural product has been identified as possessing (4R,6R) absolute configuration. Binding of the conioidine diastereomers to calf thymus DNA (CT DNA) and human serum albumin (HSA) has been investigated by fluorescence spectroscopy and isothermal titration calorimetry (ITC). All stereoisomers display at least an order of magnitude weaker binding to DNA than the control compound netropsin; however, a strong association with HSA was observed for the (4R,6S) stereoisomer.
- Shaktah, Ryan,Vardanyan, Laura,David, Elroma,Aleman, Alexis,Orr, Dupre,Shaktah, Lawrence A.,Tamae, Daniel,Minehan, Thomas
-
supporting information
p. 3191 - 3198
(2020/11/03)
-
- Pyrrolidine-Oxadiazolone Conjugates as Organocatalysts in Asymmetric Michael Reaction
-
Pyrrolidine-oxadiazolone based organocatalysts are envisaged, synthesized, and utilized for asymmetric Michael reactions. Results of the investigations suggest that some of the catalysts are indeed efficient for stereoselective 1,4-conjugated Michael additions (dr: >97:3, ee up to 99%) in high chemical yields (up to 97%) often in short reaction time. As an extension, one enantiopure Michael adduct has been utilized to synthesize optically active octahydroindole.
- Mahato, Chandan K.,Mukherjee, Sayan,Kundu, Mrinalkanti,Pramanik, Animesh
-
p. 1053 - 1063
(2019/01/14)
-
- Targeting a Large Active Site: Structure-Based Design of Nanomolar Inhibitors of Trypanosoma brucei Trypanothione Reductase
-
Trypanothione reductase (TR) plays a key role in the unique redox metabolism of trypanosomatids, the causative agents of human African trypanosomiasis (HAT), Chagas’ disease, and leishmaniases. Introduction of a new, lean propargylic vector to a known class of TR inhibitors resulted in the strongest reported competitive inhibitor of Trypanosoma (T.) brucei TR, with an inhibition constant Ki of 73 nm, which is fully selective against human glutathione reductase (hGR). The best ligands exhibited in vitro IC50 values (half-maximal inhibitory concentration) against the HAT pathogen, T. brucei rhodesiense, in the mid-nanomolar range, reaching down to 50 nm. X-Ray co-crystal structures confirmed the binding mode of the ligands and revealed the presence of a HEPES buffer molecule in the large active site. Extension of the propargylic vector, guided by structure-based design, to replace the HEPES buffer molecule should give inhibitors with low nanomolar Ki and IC50 values for in vivo studies.
- De Gasparo, Raoul,Diederich, Fran?ois,Halgas, Ondrej,Harangozo, Dora,Kaiser, Marcel,Krauth-Siegel, R. Luise,Pai, Emil F.
-
supporting information
(2019/08/21)
-
- TiO2@UiO-68-CIL: A Metal-Organic-Framework-Based Bifunctional Composite Catalyst for a One-Pot Sequential Asymmetric Morita-Baylis-Hillman Reaction
-
A chiral ionic liquid (CIL) moiety of a l-pyrrolidin-2-ylimidazole-decorated homochiral UiO-68-type metal-organic framework, UiO-68-CIL (1), was successfully prepared by the combination of a new premodified chiral CIL ligand (H2L-CIL) and ZrCl4 via a solvothermal method. The TiO2-loaded TiO2@UiO-68-CIL (2) was prepared by impregnating 1 in a toluene solution of Ti(OPri)4 and sequential in situ hydrolysis. The obtained 2 can be a bifunctional asymmetric heterogeneous catalyst to successfully promote the one-pot Morita-Baylis-Hillman reaction starting from aromatic alcohols in a tandem way.
- Hu, Yu-Hong,Liu, Cong-Xue,Wang, Jian-Cheng,Ren, Xiu-Hui,Kan, Xuan,Dong, Yu-Bin
-
supporting information
p. 4722 - 4730
(2018/10/24)
-
- PYRIDAZINONES AS PARP7 INHIBITORS
-
The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.
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-
Paragraph 1138; 1139
(2019/11/11)
-
- Prolinamides of Aminouracils, Organocatalyst Modifiable by Complementary Modules
-
We report the synthesis and evaluation of prolinamide organocatalysts that incorporate aminouracils. The features of these catalysts are enhanced NH acidity of the amide because of the electron-withdrawing nature of the heterocycle, an additional hydrogen-bond donor at the α or β positions of this functional group (using 6-aminouracil or 5,6-diaminouracil respectively), and it can be recovered due to its low solubility and used again without decreasing the enantioselectivity. A unique feature of these systems is the self-assembly capability with complementary modules by Watson–Crick interactions. These supramolecular adducts behave differently from the catalyst alone, some of them have lower performance but others improve the selectivity of the product. Therefore, this approach avoids the synthesis of many catalysts.
- Ruíz-Pérez, Karen M.,Quiroz-García, Beatriz,Hernández-Rodríguez, Marcos
-
p. 5763 - 5772
(2018/11/10)
-
- Novel pyrido[2,3-b]indole compounds for the treatment and prophylaxis of bacterial infection
-
The present invention relates to novel compounds of formula (I), wherein R1, R2, R3, R4, R5 and R6 are as described herein, and their pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
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Page/Page column 135
(2018/10/25)
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- Bifunctional composite catalyst, preparation method therefor and application of bifunctional composite catalyst
-
The invention discloses a bifunctional composite catalyst, a preparation method therefor and an application of the bifunctional composite catalyst. The bifunctional composite catalyst is of a metal-organic frame structure and has the structural formula of [Zr6O4(OH)4L6.3.8TiO2]n, wherein n is a nonzero natural number; and L has a structural formula shown in the description, wherein X is chloro-, bromo- or iodo-. The catalyst can be used for effectively catalyzing one-pot series oxidation and Morita-Baylis-Hillman reaction of p-methoxybenzyl alcohol without tedious multistep reaction and a variety of catalysts, thus, the wasting of reagents is reduced, the consumption of the catalysts is reduced, and the reaction temperature is moderate; and the catalyst is relatively clean due to no otheradditive and can be cyclically utilized for five times or more.
- -
-
Paragraph 0066; 0072; 0073
(2018/11/22)
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- C-3 NOVEL TRITERPENONE WITH C-28 AMIDE DERIVATIVES AS HIV INHIBITORS
-
The invention relates to C-3 novel triterpenone with C-28 amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases (formula 1).
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-
Paragraph 0130; 0131
(2018/09/12)
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- REDUCTION OF PRO-INFLAMMATORY HDL USING A LEUKOTRIENE INHIBITOR
-
A method involving the administration of a therapeutically effective amount of a leukotriene inhibitor, a pharmaceutically acceptable salt, a pharmaceutically acceptable N-oxide, a pharmaceutically active metabolite, a pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof to a human for reducing a level of pro-inflammatory HDL in the human. Various examples of leukotriene inhibitors, including 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin- 3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2, 2-dimethyl-propionic acid, are disclosed for administration for the reduction of pro-inflammatory HDL in a human. Reduction of pro-inflammatory HDL by the leukotriene inhibitor may include conversion of at least a portion of pro-inflammatory HDL to anti-inflammatory HDL.
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-
Paragraph 00190
(2018/09/12)
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- AMINOPYRIDINE COMPOUNDS AND METHODS FOR THE PREPARATION AND USE THEREOF
-
The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis, including its proteases arginine gingipain A/B (Rgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I and Formula III, as described herein, and pharmaceutically acceptable salts thereof.
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-
Paragraph 0279; 0336; 0343; 0393
(2018/12/02)
-
- NOVEL BETULINIC SUBSTITUTED AMIDE DERIVATIVES AS HIV INHIBITORS
-
The present invention relates to novel betulinic substituted amide compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y, Z1, Z2, Z3 and are Formula (II) as defined herein. The invention novel betulinic substituted amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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-
-
- Enantioselective Synthesis of 6,6-Disubstituted Pentafulvenes Containing a Chiral Pendant Hydroxy Group
-
Simple enantioselective synthesis of 6,6-disubstituted pentafulvenes bearing chiral pendant hydroxy groups are attained by cascade reactivity using commercially available proline-based organocatalysts. Condensation of cyclopentadiene with the acetyl function of a 1,2-formylacetophenone, followed by cyclization of a resulting fulvene-stabilized carbanion with the formyl group, generates bicyclic chiral alcohols with initial er values up to 94:6. Exceptional enantio-enrichment of the resultant alcohols results upon crystallization—even near racemic samples spontaneously de-racemize. This enables new families of substituted cyclopentadienes that are both enantiomerically and diastereomerically pure to be rapidly attained.
- Nouch, Ryan,Cini, Melchior,Magre, Marc,Abid, Mohammed,Diéguez, Montserrat,Pàmies, Oscar,Woodward, Simon,Lewis, William
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p. 17195 - 17198
(2017/11/27)
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- 2-ACYLAMINOTHIAZOLE DERIVATIVE OR SALT THEREOF
-
To provide a compound useful as an active ingredient of a pharmacological composition for the treatment of urinary storage symptoms, dysuria, lower urinary tract diseases, and the like. [Solution] The inventors perfected the present invention after discov
- -
-
Paragraph 0185
(2017/04/23)
-
- Solvent free, fast and asymmetric Michael additions of ketones to nitroolefins using chiral pyrrolidine–pyridone conjugate bases as organocatalysts
-
New chiral organocatalysts are envisaged based on a pyrrolidine–pyridone conjugate and synthesized from commercially available proline employing standard protocols. These catalysts were found to be useful for asymmetric Michael additions of ketones to nitroolefins to afford the desired products in very good yields (up to 98%) with excellent diastereo- and enantioselectivities (>97:3 syn/anti and up to 98% ee) in very short reaction time compared with the existing reports.
- Mahato, Chandan K.,Kundu, Mrinalkanti,Pramanik, Animesh
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p. 511 - 515
(2017/04/28)
-
- 2-ACYLAMINOTHIAZOLE DERIVATIVE AND SALT THEREOF
-
[Problem] A compound which is useful as an active ingredient of a pharmaceutical composition for treating storage dysfunctions, voiding dysfunctions, and lower urinary tract diseases is provided. [Means for Solution] The present inventors have found that a thiazole derivative having pyrazine-2-carbonylamino substituted at the 2-position is an excellent muscarinic M3 receptor positive allosteric modulator, and is useful as an agent for preventing and/or treating bladder or urinary tract diseases, related to bladder contraction by a muscarinic M3 receptor, thereby completing the present invention. The 2-acylaminothiazole derivative or a salt thereof of the present invention can be used as an agent for preventing and/or treating bladder or urinary tract diseases, related to bladder contraction by a muscarinic M3 receptor, for example, voiding dysfunctions such as underactive bladder.
- -
-
-
- Pyrrolidine modified PANF catalyst for asymmetric Michael addition of ketones to nitrostyrenes in aqueous phase
-
Three chiral pyrrolidine functionalized polyacrylonitrile fiber catalysts have been designed, prepared, and evaluated for their catalytic performance in asymmetric Michael addition of ketones to nitrostyrenes in water. With the optimized catalysts and conditions in hand, their reaction scope for nitrostyrenes was explored. Then the fiber catalysts were further applied to a packed-bed reactor for continuous-flow Michael addition. Based on the fact that organic solvent can inhibit the catalytic activity, a novel microenvironment catalytic mechanism is proposed.
- Du, Jianguo,Shuai, Bin,Tao, Minli,Wang, Guangwei,Zhang, Wenqin
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p. 2625 - 2631
(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 0851-0852
(2016/11/24)
-
- AUTOPHAGY-INHIBITING COMPOUNDS AND USES THEREOF
-
The present disclosure describes a compound for use in the treatment of cancer, infectious disease, and autoimmune disorders. The compounds herein can inhibit autophagy in an affected cell to promote cell death. Further, the compound can be used to overco
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-
Paragraph 00276
(2017/04/04)
-
- Synthesis of (+)-Ipalbidine Based on 6-exo-trig Radical Cyclization of a β-Amino Radical
-
N-Boc (S)-proline was converted into (2S)-2-[(phenylselanyl)methyl]pyrrolidine, which was alkylated on nitrogen with 2-bromo-1-(4-methoxyphenyl)ethan-1-one. Reaction with vinyllithium, 6-exo-trig radical cyclization (Bu3SnH, AIBN, PhMe, 110 °C), dehydration (P2O5, H3PO4), and demethylation (BBr3) gave (+)-ipalbidine with ee >99%.
- Chea, JongMyoung,Clive, Derrick L. J.
-
p. 10294 - 10298
(2015/11/03)
-
- 2-ACYLAMINOTHIAZOLE DERIVATIVE AND SALT THEREOF
-
[Problem] A compound which is useful as an active ingredient of a pharmaceutical composition for treating storage dysfunctions, voiding dysfunctions, and lower urinary tract diseases is provided. [Means for Solution] The present inventors have found that a thiazole derivative having pyrazine-2-carbonylamino substituted at the 2-position is an excellent muscarinic M 3 receptor positive allosteric modulator, and is useful as an agent for preventing and/or treating bladder or urinary tract diseases, related to bladder contraction by a muscarinic M 3 receptor, thereby completing the present invention. The 2-acylaminothiazole derivative or a salt thereof of the present invention can be used as an agent for preventing and/or treating bladder or urinary tract diseases, related to bladder contraction by a muscarinic M 3 receptor, for example, voiding dysfunctions such as underactive bladder.
- -
-
Paragraph 0410; 0411
(2016/10/07)
-
- Synthesis and in vivo evaluation of 11C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl} amide
-
Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers because of their hydrophobic character, spherical structure, and excellent chemical and photochemical stability. In the present paper, the synthesis and in vivo evaluation of 11C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N- {[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide, an analog of the D2 receptor ligand [11C]raclopride, is described. The radiosynthesis was approached by reaction of the demethylated precursor with [11C] CH3I in basic media; moderate radiochemical yields (18.2 ± 2.8%, decay corrected), and excellent radiochemical purities (>98%) were obtained in overall synthesis time of ~50 min. In vivo assays showed a biodistribution pattern with significant uptake in liver, kidneys and lungs at short times (t = 4 min) after administration and increasing accumulation in bladder at longer times (t ≥ 14.5 min). Although brain positron emission tomography scans showed good blood brain barrier penetration, the high unspecific uptake observed in different brain regions impedes its applicability as D2 receptor ligand.
- G?mez-Vallejo, Vanessa,Vázquez, Naiara,Gona, Kiran Babu,Puigivila, Maria,González, Mikel,Sebastián, Eneko San,Martin, Abraham,Llop, Jordi
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p. 209 - 214
(2014/05/06)
-
- METHODS OF TREATING LIVER DISEASES
-
The invention provides tricyclic compounds and their use in treating liver disorders, such as non-alcoholic steatohepatitis and related disorders (e.g., fibrosis). The compounds are contemplated to have activity against methionyl aminopeptidase 2.
- -
-
Paragraph 00411
(2014/05/24)
-
- (2 S)-2-[(Phenylsulfinyl)methyl]pyrrolidine-catalyzed efficient stereoselective michael addition of cyclohexanone and cyclopentanone to nitroolefins
-
(2S)-2-[(Phenylsulfinyl)methyl]pyrrolidine, derived from l-proline, has been demonstrated as an efficient organocatalyst for the asymmetric Michael addition of cyclohexanone and cyclopentanone to β-nitrostyrenes. This pyrrolidine-based catalyst bearing a sulfoxide moiety was used to synthesize various γ-nitro carbonyl compounds in high yield (up to 97%) with excellent stereoselectivity (up to >99:1 dr and >99% ee) without the use of any additive.
- Singh, Kamalnain,Singh, Paramjit,Kaur, Amarjit,Singh, Pushpinder,Sharma, Sandeepkumar,Khullar, Sadhika,Mandal, Sanjay K.
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p. 1406 - 1413
(2013/07/05)
-
- Synthesis of new enantiopure thioureas derived from (S)-proline
-
Enantiopure thiourea derivatives, containing pyrrolidine ring, were prepared by the reaction of N-Boc-(S)-2-aminomethylpyrrolidine (6) with thioisocyanates 8.
- Wroblewska, Aneta,Mloston, Grzegorz
-
p. 509 - 511
(2013/07/25)
-
- Design, synthesis and catalytic property of L-proline derivatives as organocatalysts for direct aldol reaction
-
A series of chiral prolinamide compounds with pyridine-2, 6-dicarboxylic acid moieties derived from L-proline have been designed and synthesized, their catalytic properties for direct asymmetric aldol reactions were also studied in this article. These catalysts gave the aldol product in high yield (87%) and high enantioselectivity, up to 85%, of the anti-structure at room temperature but gave disappointing results at a lower temperature or when additive was added. Conditions, including solvents, temperature and additives were screened for the reactions. Moreover, the influence of presence of water on yield and stereoselectivity was also discussed. Copyright
- Wang, Lei,Tang, Ruiren,Yang, Hua
-
p. 591 - 598
(2013/11/06)
-
- A new class of fluorinated 5-pyrrolidinylsulfonyl isatin caspase inhibitors for PET imaging of apoptosis
-
Thirteen compounds in a new class of fluorinated 5-pyrrolidinylsulfonyl isatin derivatives were synthesised that have potent and selective inhibitory activity against effector caspases-3 and -7. With in vivo animal PET imaging studies of cerebral ischemia being planned, N-benzylation with selected para-substituted benzylic halides allowed systematic variation of lipophilicity (logP 1.94-3.31) without decreasing inhibition potency (IC50). From this series the p-methoxybenzyl analogue was selected for initial 'proof-of-concept' [18F]-fluoride radiolabelling which proceeded in good yield and purity with no need for a protection/deprotection strategy. The Royal Society of Chemistry.
- Krause-Heuer, Anwen M.,Howell, Nicholas R.,Matesic, Lidia,Dhand, Geetanjali,Young, Emma L.,Burgess, Leena,Jiang, Cathy D.,Lengkeek, Nigel A.,Fookes, Christopher J. R.,Pham, Tien Q.,Sobrio, Franck,Greguric, Ivan,Fraser, Benjamin H.
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p. 347 - 352
(2013/06/04)
-
- Chiral aminophosphines as catalysts for enantioselective double-michael indoline syntheses
-
The bisphosphine-catalyzed double-Michael addition of dinucleophiles to electron-deficient acetylenes is an efficient process for the synthesis of many nitrogencontaining heterocycles. Because the resulting heterocycles contain at least one stereogenic center, this double-Michael reaction would be even more useful if an asymmetric variant of the reaction were to be developed. Aminophosphines can also facilitate the double-Michael reaction and chiral amines are more readily available in Nature and synthetically; therefore, in this study we prepared several new chiral aminophosphines. When employed in the asymmetric double-Michael reaction between ortho-tosylamidophenyl malonate and 3-butyn-2-one, the chiral aminophosphines produced indolines in excellent yields with moderate asymmetric induction.
- Khong, San N.,Kwon, Ohyun
-
p. 5626 - 5650
(2012/07/03)
-
- PARTIALLY SATURATED TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME
-
The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
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-
Page/Page column 180; 181
(2012/12/13)
-
- Synthesis of chiral NADH analog based on proline template including thiourea and nicotinic acid moieties
-
Chiral reductase-mimicking organic molecule built on proline template incorporating a covalently bound NADH mimic via thiourea, and related reducing agent Hantzsch dihydropyridine, was designed. A synthetic path was developed involving interlinking of chiral proline derivatives with thiourea and subsequent coupling reaction with nicotinoyl chloride. The structure of target compound was studied by x-ray, indicating a double H bond with thiourea hydrogens and oxygen O1 of benzylcarbamate fragment. The reduction of benzil and imines was performed. Taylor & Francis Group, LLC.
- Bagdziunas, Gintautas,Haukka, Matti,Butkus, Eugenijus
-
p. 2517 - 2523
(2011/08/07)
-
- Proline-derived aminotriazole ligands: Preparation and use in the ruthenium-catalyzed asymmetric transfer hydrogenation
-
The preparation of 2-triazolyl- and 2-triazolylmethylpyrrolidines from L-proline and L-trans-4-hydroxyproline is described, along with their evaluation as chiral ligands in ruthenium-catalyzed asymmetric transfer hydrogenation. Modular evolution of the ligands by introduction of remote substituents is also presented, showing a surprisingly important effect on the performance of the ligands.
- Cambeiro, Xacobe C.,Pericas, Miquel A.
-
p. 113 - 124
(2011/04/12)
-
- Synthesis of D2 receptor ligand analogs incorporating one dicarba-closo-dodecaborane unit
-
Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers. In the current Letter, analogs of enantiomeric substituted benzamides (Raclopride and FLB-457) in which the phenyl ring has been substituted by a carborane cage (either orto- or meta-carborane) have been developed as potential D2 receptor antagonists. The formation of intramolecular hydrogen bonds (in solution) and the stability of the new chemical entities have been evaluated by means of 1H NMR and HPLC-MS, respectively.
- Vázquez, Naiara,Gómez-Vallejo, Vanessa,Calvo, Javier,Padro, Daniel,Llop, Jordi
-
p. 615 - 618
(2011/03/18)
-
- N-ACYL CYCLIC AMINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
-
The present invention provides compounds which show high effectiveness against positive symptoms, negative symptoms and cognitive dysfunction in schizophrenia and reduce conventional side-effect risks as well as have remarkable effects for central neurolo
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-
Page/Page column 64
(2011/10/05)
-
- PROCESS FOR PREPARING 4- { (S) -2- (4-(4-CHLOROPHENOXY) PHENOXYMETHYL) PYRROLIDIN-1-YL) } BUTYRIC ACID AND SALTS THEREOF
-
The present invention relates to a process for preparing 4-{(S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyric acid and its salts.
- -
-
Page/Page column 15
(2011/02/24)
-
- A chiral pyrrolidine-pyrazole catalyst for the enantioselective Michael addition of carbonyls to nitroolefins
-
An enantioselective Michael reaction of carbonyl compounds to nitroolefins has been accomplished using a novel chiral pyrrolidine-pyrazole catalyst. This newly prepared catalyst was found to be very effective in providing good yields as well as good diast
- Chandrasekhar, Srivari,Kumar, Togapur Pavan,Haribabu, Kothapalli,Reddy, Chada Raji,Kumar, Chitumalla Ramesh
-
scheme or table
p. 697 - 702
(2011/07/09)
-
- Discovery of 4-[(2S)-2-{[4-(4-Chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl] butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis
-
Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA4H) as a key target for the treatment of cardiovascular disease. We combined fragmentbased crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA4H. Ligand efficiency was followed throughout our structure-activity studies. As applied within the context of LTA4H inhibitor design, the chemistry team was able to design a potent compound 20 (DG-051) (Kd=26 nM) with high aqueous solubility (>30 mg/mL) and high oral bioavailability (>80% across species) that is currently undergoing clinical evaluation for the treatment of myocardial infarction and stroke. The structural biology-chemistry interaction described in this paper provides a sound alternative to conventional screening techniques. This is the first example of a gene-to-clinic paradigm enabled by a fragment-based drug discovery effort.
- Sandanayaka, Vincent,Mamat, Bjorn,Mishra, Rama K.,Winger, Jennifer,Krohn, Michael,Zhou, Li-Ming,Keyvan, Monica,Enache, Livia,Sullins, David,Onua, Emmanuel,Zhang, Jun,Halldorsdottir, Gudrun,Sigthorsdottir, Heida,Thorlaksdottir, Audur,Sigthorsson, Gudmundur,Thorsteinnsdottir, Margret,Davies, Douglas R.,Stewart, Lance J.,Zembower, David E.,Andresson, Thorkell,Kiselyov, Alex S.,Singh, Jasbir,Gurney, Mark E.
-
experimental part
p. 573 - 585
(2010/07/09)
-
- Functionalized proline with double hydrogen bonding potential: Highly enantioselective Michael addition of carbonyl compounds to β-nitrostyrenes in brine
-
Simple synthetic manipulation of S-proline allows access to prolinamides 5-7 as organocatalysts capable of double hydrogen bonding for enantioselective Michael addition reactions of carbonyl compounds to β-nitrostyrenes. It is shown that prolinamide catalyst 7 leads to addition products with a high diastereo- as well as enantioselectivity. The transition state structure involving the binding of electrophilic nitrostyrene via two H-bonds is believed to be further stabilized by π,π stacking interactions mediated by the tosyl ring.
- Saha, Satyajit,Seth, Saona,Moorthy, Jarugu Narasimha
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supporting information; experimental part
p. 5281 - 5286
(2010/11/03)
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- Chiral quaternary alkylammonium ionic liquid [Pro-dabco][BF4]: As a recyclable and highly efficient organocatalyst for asymmetric Michael addition reactions
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A novel series of chiral quaternary ammonium ionic liquids have been synthesized and shown to be very effective catalysts for the asymmetric Michael addition reactions of ketones and aldehydes to nitroolefins with excellent yields (up to 100%), diastereos
- Xu, Da-Zhen,Liu, Yingjun,Shi, Sen,Wang, Yongmei
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experimental part
p. 2530 - 2534
(2011/03/17)
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- Recyclable merrifield resin-supported organocatalysts containing pyrrolidine unit through A3-coupling reaction linkage for asymmetric michael addition
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Merrifield resin-supported pyrrolidine-based chiral organocatalysts A2D through A3-coupling reaction linkage have been developed and found to be highly effective catalysts for the Michael addition reaction of ketones with nitrostyrenes. The rea
- Liu, Jie,Li, Pinhua,Zhang, Yicheng,Ren, Kai,Wang, Lei,Wang, Guanwu
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experimental part
p. 432 - 441
(2012/04/23)
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- Asymmetric organocatalysis of the addition of acetone to 2-nitrostyrene using N-diphenylphosphinyl-1,2-diphenylethane-1,2-diamine (PODPEN)
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The highly enantioselective addition of acetone to 2-nitrostyrene, using N-diphenylphosphinyl-trans-1,2-diphenylethane-1,2-diamine (PODPEN) as a catalyst, is described.
- Morris, David J.,Partridge, A. Simon,Manville, Charles V.,Racys, Daugidas T.,Woodward, Gary,Docherty, Gordon,Wills, Martin
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supporting information; experimental part
p. 209 - 212
(2010/03/24)
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- ANTIFUNGAL AGENTS
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Novel derivatives of enfumafungin are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antifungal agents and/or inhibitors of (l,3)-β-D-glucan synthase. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs,,as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating and/or preventing fungal infections and associated diseases and conditions.
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Page/Page column 67-68
(2010/04/03)
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- ANTIFUNGAL AGENTS
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Novel derivatives of enfumafungin are disclosed herein, along with' their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and method of using such compounds as antifungal agents and/or inhibitors of (l,3)-β-D-glucan synthase. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating and/or preventing fungal infections and associated diseases and conditions.
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Page/Page column 54
(2010/04/03)
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- 5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)-A potent FLAP inhibitor
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A series of potent 5-lipoxygenase-activating protein (FLAP) inhibitors are herein described. SAR studies focused on the discovery of novel alicyclic moieties appended to an indole core to optimize potency, physical properties and off-target activities. Subsequent SAR on the N-benzyl substituent of the indole led to the discovery of compound 39 (AM679) which showed potent inhibition of leukotrienes in human blood and in a rodent bronchoalvelolar lavage (BAL) challenge model.
- Stock, Nicholas,Baccei, Christopher,Bain, Gretchen,Broadhead, Alex,Chapman, Charles,Darlington, Janice,King, Christopher,Lee, Catherine,Li, Yiwei,Lorrain, Daniel S.,Prodanovich, Pat,Rong, Haojing,Santini, Angelina,Zunic, Jasmine,Evans, Jilly F.,Hutchinson, John H.,Prasit, Peppi
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scheme or table
p. 213 - 217
(2010/04/24)
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- ISATIN ANALOGUES AND USES THEREFOR
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Novel isatin analogues, including isatin analogues comprising Michael Acceptors (IMAs) are disclosed. Further disclosed are methods of synthesis of the isatin analogues, and uses of the analogues, including inhibition of caspase-3 and caspase-7, and in vi
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Page/Page column 9
(2009/04/24)
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- Synthesis and structural assignment of two major metabolites of the LTA4H inhibitor DG-051
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The same two major CYP mediated metabolites of DG-051 were produced in the presence of rat, dog, monkey and human liver microsomes. Their respective structures were hypothesized based on mass spectrometry data correlated with the parent structure and conf
- Enache, Livia A.,Zhang, Jun,Sullins, David W.,Kennedy, Isaac,Onua, Emmanuel,Zembower, David E.,Muellner, Frank W.,Singh, Jasbir,Kiselyov, Alex S.
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scheme or table
p. 6275 - 6279
(2010/06/13)
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- Development of a scalable synthetic process for DG-051B, a first-in-class inhibitior of LTA4H
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DG-051B is a first-in-class small molecule inhibitor of leukotriene A4 hydrolase (LTA4H), currently in Phase II clinical development for the prevention of heart attack. Process optimization led from a linear seven-step synthetic procedure to a convergent
- Enache, Livia A.,Kennedy, Isaac,Sullins, David W.,Chen, Wei,Ristic, Dragan,Stahl, Glenn L.,Dzekhtser, Sergey,Erickson, Robert A.,Yan, Changren,Muellner, Frank W.,Krohn, Michael D.,Winger, Jennifer,Sandanayaka, Vincent,Singh, Jasbir,Zembower, David E.,Kiselyov, Alex S.
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experimental part
p. 1177 - 1184
(2010/04/22)
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