- Fmoc-protected iminosugar modified asparagine derivatives as building blocks for glycomimetics-containing peptides
-
CSF114(Glc) is the first synthetic Multiple Sclerosis Antigenic Probe able to identify autoantibodies in a statistically significant number of Multiple Sclerosis patients. The β-turn conformation of this glucopeptide is fundamental for a correct presentat
- Nuti, Francesca,Paolini, Ilaria,Cardona, Francesca,Chelli, Mario,Lolli, Francesco,Brandi, Alberto,Goti, Andrea,Rovero, Paolo,Papini, Anna M.
-
-
Read Online
- Synthesis of Three-Dimensional (Di)Azatricyclododecene Scaffold and Its Application to Peptidomimetics
-
A novel sp3 carbon-rich tricyclic 3D scaffold-based peptide mimetic compound library was constructed to target protein-protein interactions. Tricyclic framework 7 was synthesized from 9-azabicyclo[3,3,1]nonan-3-one (11) via a gold(I)-catalyzed Conia-ene reaction. The electron-donating group on the pendant alkyne of cyclization precursor 12 b–e was the key to forming 6-endo-dig cyclized product 7 with complete regioselectivity. Using the synthetic strategy for regioselective construction of bridged tricyclic framework 7, a diazatricyclododecene 3D-scaffold 8 a, which enables the introduction of substituents into the scaffold to mimic amino acid side chains, was designed and synthesized. The peptide mimetics 21 a–u were synthesized via step-by-step installation of three substituents on diazatricyclododecene scaffold 8 a. Compounds 21 a–h were synthesized as α-helix peptide mimics of hydrophobic ZZxxZ and ZxxZZ sequences (Z=Leu or Phe) and subjected to cell-based assays: antiproliferative activity, HIF-1 transcriptional activity which is considered to affect cancer malignancy, and antiviral activity against rabies virus. Compound 21 a showed the strongest inhibitory activity of HIF-1 transcriptional activity (IC50=4.1±0.8 μM), whereas compounds 21 a–g showed antiviral activity with IC50 values of 4.2–12.4 μM, suggesting that the 3D-scaffold 8 a has potential as a versatile peptide mimic skeleton.
- Katoh, Akira,Kouji, Hiroyuki,Morita, Taiki,Nakamura, Hiroyuki,Umedera, Kohei,Yamada, Kentaro,Yoshimori, Atsushi
-
supporting information
p. 11888 - 11894
(2021/07/06)
-
- Compound JK-03M having higher protein kinase G inhibitory activity or pharmaceutically acceptable salt thereof and preparation method thereof
-
The invention discloses a compound which has higher protein kinase G inhibitory activity and is shown in a formula I or pharmaceutically acceptable salt thereof and a preparation method thereof. The compound JK-03M having the higher protein kinase G inhibitory activity comprises a pharmaceutical composition of a new compound and application of the new compound in treatment of pain, in particular to chronic pain. The formula (1) is shown in the description.
- -
-
Paragraph 0093; 0118; 0130-0132
(2018/11/03)
-
- Synthesis and α-glucosidase inhibition activity of dihydroxy pyrrolidines
-
A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides of 3,4-dihydroxypyrrolidines as α-glucosidase inhibitors were designed and synthesized. The biological screening test against α-glucosidase showed that some of these compounds have the positive inhibitory activity against α-glucosidase. Saturated aliphatic amides were more potent than the olefinic amides. Among all the compounds, 5o/6o having polar –NH2 group, 10f/11f having polar –OH group on phenyl ring displayed 3–4-fold more potent than the standard drugs. Acarbose, Voglibose and Miglitol were used as standard references. The promising compounds 6i, 5o, 6o, 10a, 11a, 10f and 11f have been identified. Molecular docking simulations were done for compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.
- Kasturi, Sivaprasad,Surarapu, Sujatha,Uppalanchi, Srinivas,Anireddy, Jaya Shree,Dwivedi, Shubham,Anantaraju, Hasitha Shilpa,Perumal, Yogeeswari,Sigalapalli, Dilep Kumar,Babu, Bathini Nagendra,Ethiraj, Krishna S.
-
supporting information
p. 2818 - 2823
(2017/05/29)
-
- Compounds with higher PKG (protein kinase G) inhibitory activity and preparation method of compounds
-
The invention discloses compounds which have higher PKG (protein kinase G) inhibitory activity and are represented as a formula I, pharmaceutically acceptable salts, pharmaceutical composition containing the novel compounds, as well as an application of the novel compounds in treatment of pain, especially chronic pain. The invention further discloses a preparation method of the compounds and new intermediates. R1 and R2 are the same or different and are selected from a group comprising halogen (such as F or Cl), C1-C6 alkoxy, C1-C6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl; R3 is a terminal group and is selected from a group comprising H, halogen, alkyl, naphthenic base, alkenyl, alkynyl, aryl and heteroaryl; n is the number of repetitive units and is an integer in a range from 1 to 15.
- -
-
Paragraph 0154; 0155; 0156; 0157; 0158; 0159
(2016/10/08)
-
- COMPOUND HAVING HIGHER INHIBITION OF PROTEIN KINASE G ACTIVITY AND PREPARATION METHOD THEREFOR
-
Disclosed are a compound of Formula I having higher inhibition of protein kinase G (PKG) activity and pharmaceutically acceptable salts thereof. In Formula I, R1 and R2 are the same or different, each being independently chosen from the halogens, the C1-C6 alkoxyl group, the C1-C6 alkyl group, the C2-C6 alkenyl group, and the C2-C6 alkynyl group; R3 is chosen from H, the halogens, the substituted or unsubstituted C1-C6 alkyl group, C3-C6 cycloalkyl group, C2-C6 alkenyl group, and C2-C6 alkynyl group, aryl group, and heteroaryl group; and n is an integer between 0 and 15. Also disclosed is a pharmaceutical composition comprising said compound, the use of the compound in treating pains, in particular chronic pain, a preparation method for the compound, and a new intermediate.
- -
-
Paragraph 0073; 0074
(2016/12/12)
-
- Five-membered iminocyclitol α-glucosidase inhibitors: Synthetic, biological screening and in silico studies
-
The design and synthesis of a small library of pyrrolidine iminocyclitol inhibitors with a structural similarity to 1,4-dideoxy-1,4-imino-d-arabitol (DAB-1) is reported. This library was specifically designed to gain a better insight into the mechanism of inhibition of glycosidases by polyhydroxylated pyrrolidines or iminocyclitols. Pyrrolidine-3,4-diol 15a and pyrrolidine-3,4-diol diacetate 15b had emerged as the most potent α-glucosidase inhibitors in the series. Docking studies performed with an homology model of α-glucosidase disclosed binding poses for compounds 15a, 15b, 16a, and 16a′ occupying the same region as the NH group of the terminal ring of acarbose and suggest a closer and stronger binding of compound 15a and 15b with the enzyme active site residues. Our studies indicate that 2 or 5-hydroxyl substituents appear to be vital for high inhibitory activity.
- Guerreiro, Luis R.,Carreiro, Elisabete P.,Fernandes, Luis,Cardote, Teresa A.F.,Moreira, Rui,Caldeira, Ana T.,Guedes, Rita C.,Burke
-
p. 1911 - 1917
(2013/04/23)
-
- COFERONS AND METHODS OF MAKING AND USING THEM
-
The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes one or more pharmacophores which potentially binds to a target molecule with a dissociation constant of less than 300 μM and a linker element connected to the pharmacophore. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to the pharmacophore.
- -
-
Page/Page column 170
(2012/12/13)
-
- NOVEL PYRROLOY2,3-d¨PYRIMIDINE COMPOUND
-
Disclosed is a novel pyrrolo[2,3-d]pyrimidine compound represented by formula [I] or a pharmacologically acceptable salt thereof, which has a GPR119 receptor agonistic activity and is useful for a pharmaceutical. In formula [I], E represents a group repre
- -
-
Page/Page column 86
(2011/12/12)
-
- SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS
-
Provided are compositions and methods useful for modulation of signaling through the Toll- like receptors TLR7 and/or TLR8. The compositions and methods have use in treating or preventing disease, including cancer, autoimmune disease, infectious disease, inflammatory disorder, graft rejection, and graft-verses-host disease.
- -
-
Page/Page column 79
(2011/04/13)
-
- Synthesis of iminodiacetaldehyde derivatives as building blocks for pharmacologically active agents
-
The preparation of iminodiacetaldehyde derivatives is reported via oxidative cleavage of 3,4-dihydroxypyrrolidines with sodium periodate. High yields of iminodiacetaldehydes are obtained starting from N-acyl-protected pyrrolidines, whereas the basic N-benzyl-protected derivative does not yield the expected dialdehyde. A cis-configured dihydroxypyrrolidine, prepared from 2,5-dihydropyrrole, reacts considerably faster with sodium periodate than the corresponding trans-configured derivatives which are obtained in three steps from (R,R)-tartaric acid. Georg Thieme Verlag Stuttgart.
- Fricke, Yvonne,Kopp, Nicole,Wuensch, Bernhard
-
experimental part
p. 791 - 796
(2010/09/11)
-
- Exocyclic deoxyadenosine adducts of 1,2,3,4-diepoxybutane: Synthesis, structural elucidation, and mechanistic studies
-
1,2,3,4-Diepoxybutane (DEB) is considered the ultimate carcinogenic metabolite of 1,3-butadiene, an important industrial chemical and environmental pollutant present in urban air. Although it preferentially modifies guanine within DNA, DEB induces a large number of A → T transversions, suggesting that it forms strongly mispairing lesions at adenine nucleobases. We now report the discovery of three potentially mispairing exocyclic adenine lesions of DEB: N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′- deoxyadenosine (compound 2), 1,N6-(2-hydroxy-3-hydroxymethylpropan-1, 3-diyl) -2′-deoxyadenosine (compound 3), and 1,N6-(1- hydroxymethyl-2-hydroxypropan-1,3-diyl)-2′-deoxyadenosine (compound 4). The structures and stereochemistry of the novel DEB-dA adducts were determined by a combination of UV and NMR spectroscopy, tandem mass spectrometry, and independent synthesis. We found that synthetic N6-(2-hydroxy-3,4- epoxybut-1-yl)-2′-deoxyadenosine (compound 1) representing the product of N6-adenine alkylation by DEB spontaneously cyclizes to form 3 under aqueous conditions or 2 under anhydrous conditions in the presence of an organic base. Compound 3 can be interconverted with 4 by a reversible unimolecular pericyclic reaction favoring 4 as a more thermodynamically stable product. Both 3 and 4 are present in double stranded DNA treated with DEB in vitro and in liver DNA of laboratory mice exposed to 1,3-butadiene by inhalation. We propose that in DNA under physiological conditions, DEB alkylates the N-1 position of adenine in DNA to form N1-(2-hydroxy-3,4-epoxybut-1-yl)-adenine adducts, which undergo an SN2-type intramolecular nucleophilic substitution and rearrangement to give 3 (minor) and 4 (major). Formation of exocyclic DEB-adenine lesions following exposure to 1,3-butadiene provides a possible mechanism of mutagenesis at the A:T base pairs.
- Seneviratne, Uthpala,Antsypovich, Sergey,Goggin, Melissa,Dorr, Danae Quirk,Guza, Rebecca,Moser, Adam,Thompson, Carrie,York, Darrin M.,Tretyakova, Natalia
-
scheme or table
p. 118 - 133
(2011/02/16)
-
- Asymmetric addition of diethylzinc to ketones promoted by tartaric acid derivatives
-
The preparation of new sulfonamide ligands derived from L-tartaric acid and camphor sulfonyl chloride are described. The employment in the titanium tetraisopropoxide-promoted enantioselective addition of diethylzinc to ketones has been studied. The best enantiomeric excess is up to 99% with 7 mol% catalyst loading at room temperature. Copyright Taylor & Francis Group, LLC.
- Hui, Ailing,Zhang, Jintang,Wang, Zhiyong
-
p. 2374 - 2384
(2008/09/21)
-
- Synthesis of diastereomeric 3-hydroxy-4-pyrrolidinyl derivatives of nucleobases
-
The work deals with the synthesis of hydroxypyrrolidine analogs of nucleosides. Starting from the optically pure l- or d-tartaric acid, we improved the synthesis of enantiomeric trans-3,4-dihydroxypyrrolidines and elaborated a procedure for the synthesis of all possible diastereoisomers of 3-hydroxy-4-pyrrolidinyl derivatives of both purine and pyrimidine nucleobases. The prepared compounds were tested for cytostatic and antiviral properties but no significant activity was found.
- Rejman, Dominik,Ko?alka, Petr,Budě?ínsky, Milo?,Pohl, Radek,Rosenberg, Ivan
-
p. 1243 - 1253
(2007/10/03)
-
- Syntheses of enantiopure 3,4-diamino-1-substituted pyrrolidines
-
A convenient and general route to enantiopure 3,4-di-amino-1-substituted pyrrolidines has been devised. 1-Alkyl, 1-alkanoyl, 1-cycloalkyl and 1-aryl-3,4-diaminopyrrolidines of the (3R,4R)-configurations have all been prepared, the cycloalkyl and (mono)ary
- Marson, Charles M.,Melling, Robert C.
-
p. 247 - 256
(2007/10/03)
-
- Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors
-
Amides derived from fluorinated pyrrolidines and 4-substituted cyclohexylglycine analogues have been prepared and evaluated as inhibitors of dipeptidyl dipeptidase IV (DP-IV). Analogues which incorporated (S)-3-fluoropyrrolidine showed good selectivity for DP-IV over quiescent cell proline dipeptidase (QPP). Compound 48 had good pharmacokinetic properties and was orally active in an oral glucose tolerance test in lean mice.
- Caldwell, Charles G.,Chen, Ping,He, Jiafang,Parmee, Emma R.,Leiting, Barbara,Marsilio, Frank,Patel, Reshma A.,Wu, Joseph K.,Eiermann, George J.,Petrov, Aleksandr,He, Huaibing,Lyons, Kathryn A.,Thornberry, Nancy A.,Weber, Ann E.
-
p. 1265 - 1268
(2007/10/03)
-
- Indolyl-urea derivatives of thienopyridines useful as antiangiogenic agents, and methods for their use
-
The invention relates to compounds represented by the formula I and to prodrugs thereof, pharmaceutically acceptable salts or solvates of said compounds or said prodrugs, wherein X, R1 and R11 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.
- -
-
Page/Page column 22
(2010/02/05)
-
- Polyhydroxypyrrolidine glycosidase inhibitors related to (+)-lentiginosine1
-
(+)-Lentiginosine (14) and (7R)-7-hydroxylentiginosine (26), powerful inhibitors of amyloglucosidases, and their enantiomers were obtained in high overall yields by a multistep synthesis involving 1,3-dipolar cycloaddition of enantiopure tartaric acid derived pyrroline N-oxides. Structurally related (S,S)-3,4-dihydroxypyrrolidines 29-33 were synthesized as simpler models and tested towards 24 glycosidases.
- Cardona, Francesca,Goti, Andrea,Picasso, Sylviane,Vogel, Pierre,Brandi, Alberto
-
p. 585 - 601
(2007/10/03)
-
- Synthesis and biological evaluation of novel 1β-methylcarbapenems having a new moiety at C-2
-
The synthesis and biological activity of the novel series of 1β- methylcarbapenems 1a-f, bearing a variety of 3'',4''-disubstituted pyrrolidinamides as substituents at C-2, are described. Of these carbapenems, diol 1a showed the most potent and well balanced antibacterial activity against Gram-positive and Gram-negative, 1a was also evaluated for pharmacokinetics and in vivo therapeutic efficacy in systemic infections.
- Kang, Yong Koo,Shin, Kye Jung,Yoo, Kyung Ho,Seo, Kyung Jae,Park, Seung Yong,Kim, Dong Jin,Park, Sang Woo
-
p. 2385 - 2390
(2007/10/03)
-