- Gem-dimethyl peptide nucleic acid (α/β/γ-gdm-PNA) monomers: synthesis and the role ofgdm-substituents in preferential stabilisation ofZ/E-rotamers
-
The flexible backbone of aminoethylglycine (aeg) PNA upon substitution becomes sterically constrained to enable conformational pre-organization for preferential binding to DNA or RNA. The bulkygem-dimethyl (gdm) substituent on carbons adjacent to thet-amide sidechain either at Cα (glycyl) or Cβ/Cγ (aminoethylene) sides may influence theZ/Erotamer ratio arising from a restricted rotation around thet-amide bond. Employing 2D NMR (NOESY), it is shown here that the Cα-gdm-PNA-T monomer exhibits exclusively theZ-rotamer, while the Cβ-gdm-PNA-T monomer shows only theE-rotamer. The unsubstitutedaeg-PNA-T and Cγ-gdm-PNA-T monomers display a mixture ofZ/Erotamers. The rotamers witht-amide carbonyl pointing towards thegem-dimethyl group always prevailed. The results are supported by computational studies that suggested that the preferred rotamers are the outcome of a net energetic benefit from the stabilising n-π* interactions of carbonyls (amide backbone andt-amide sidechain), and C-H?O interactions and the destabilising steric clash ofgem-dimethyl groups with the t-amido methylene group. TheE-rotamer structure in Cγ-gdmis also characterised by X-ray crystallography. The exclusiveE-rotamer for the Cβ-gdmmonomer seen in solution here is the first such example among several modified PNA monomers. Since the conformation of the sidechain is important for inducing base stacking and effective base pairing, the exclusiveE-rotamer in the Cβ-gdmmonomer may have significance in the properties of the derived PNA?:?DNA/RNA duplexes with allE-rotamers.
- Datta, Dhrubajyoti,Ganesh, Krishna,Kulkarni, Pradnya,Ramabhadran, Raghunath O.
-
p. 6534 - 6545
(2021/08/03)
-
- ALKYLBORONIC ACIDS AS ARGINASE INHIBITORS
-
Provided are alkylboronic acids as arginase inhibitors represented by formula (I), or a pharmaceutically acceptable salt, stereoisomer, tautomer, or prodrug thereof and a pharmaceutical composition comprising said compounds.
- -
-
Page/Page column 103
(2020/08/22)
-
- NITROGENOUS HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, COMPOSITION AND USE
-
Disclosed are a nitrogenous heterocyclic compound, intermediates, a preparation method, a composition and use thereof. The nitrogenous heterocyclic compound in the present invention is as shown in formula I. The compound has a high inhibitory activity towards ErbB2 tyrosine kinase and a relatively good inhibitory activity towards human breast cancer BT-474 and human gastric cancer cell NCI-N87 which express ErbB2 at a high level, and at the same time has a relatively weak inhibitory activity towards EGFR kinase. Namely, the compound is a highly selective small-molecule inhibitor targeted at ErbB2, and hence it has a high degree of safety, and can effectively enlarge the safety window in the process of taking the drug.
- -
-
Paragraph 0192
(2019/01/17)
-
- HETEROCYCLIC COMPOUNDS AS ARGINASE INHIBITORS
-
The present invention relates to heterocyclic compounds as arginase inhibitors, in particular to a compound represented by Formula (I), or a pharmaceutically acceptable salt, stereoisomer or tautomer, or prodrug thereof and a pharmaceutical composition comprising said compound.
- -
-
Page/Page column 69
(2019/07/13)
-
- AN ADVANTAGEOUS PROCESS FOR PREPARING ANAGLIPTIN AND ITS NOVEL CRYSTALLINE FORM-H
-
The present invention discloses the process for preparation of Anagliptin and its novel crystalline form-H.
- -
-
Page/Page column 14
(2016/12/22)
-
- Compounds
-
Pyrimidone compounds of formula (I): are inhibitors of the enzyme Lp-PLA2 and are of use in treating atherosclerosis.
- -
-
Page/Page column 21
(2016/05/11)
-
- TRICYCLIC LACTAMS FOR USE IN THE PROTECTION OF NORMAL CELLS DURING CHEMOTHERAPY
-
This invention is in the area of tricyclic lactam compounds, compositions and methods of protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, protection of healthy cells is disclosed using compounds that act as cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.
- -
-
Page/Page column 89; 128; 91; 129
(2015/11/09)
-
- A PROCESS FOR THE PREPARATION OF ANAGLIPTIN AND ITS INTERMEDIATES THEREOF
-
The present invention relates to an improved process for the preparation of Anagliptin, intermediates thereof, or pharmaceutically acceptable thereof. The present invention also direct to another short process for the preparation of Anagliptin. The present invention also specifically provides an improved process for the purification of intermediate of Anagliptin. Further, the present invention relates to a polymorph of Anagliptin or a pharmaceutically acceptable salt thereof and a method for the preparation thereof.
- -
-
Page/Page column 28
(2015/12/30)
-
- Influence of achiral units with gem-dimethyl substituents on the helical character of aliphatic oligourea foldamers
-
The structures of various urea oligomers incorporating one or two central achiral 1,2-diamino-1,1-dimethylethane (DADME) units have been investigated in solution and in the crystalline state. These diamine monomers are analogous to the achiral helicogenic
- Fremaux, Juliette,Dolain, Christel,Kauffmann, Brice,Clayden, Jonathan,Guichard, Gilles
-
supporting information
p. 7415 - 7417
(2013/09/23)
-
- SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS
-
Compounds of Formula (I) and salts thereof in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.
- -
-
Page/Page column 106-107
(2011/02/24)
-
- SUBSTITUTED HETEROCYCLIC DERIVATIVES FOR THE TREATMENT OF PAIN AND EPILEPSY
-
Compounds of formula (I) which are useful in ameliorating conditions characterized by unwanted sodium and/or calcium channel activity, particularly unwanted Nav 1.7, Nav 1.8, or Cav 3.2 channel activity are disclosed. Specifically, a series of compounds containing piperidine or piperazine linked through an amide, isoxazole or similar linker to an aryl ring are described and are shown to be useful for the treatment of pain or epilepsy. A is selected from Formulae (i) or (ii).
- -
-
Page/Page column 37
(2011/04/14)
-
- COMPOUNDS FOR TREATING DISORDERS MEDIATED BY METABOTROPIC GLUTAMATE RECEPTOR 5, AND METHODS OF USE THEREOF
-
Provided herein are compounds and methods of synthesis thereof. The compounds set forth herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders, neurodegenerative disorders, neuropsychiatric disorders, disorders of cognition, learning or memory, gastrointestinal disorders, lower urinary tract disorder, and cancer. Compounds set forth herein modulate the activity of metabotropic glutamate receptor 5 (mGluR5) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.
- -
-
Page/Page column 198
(2011/07/07)
-
- 5-ALKYLOXY-INDOLIN-2-ONE DERIVATIVES, PREPARATION THEREOF AND APPLICATION THEREOF IN THERAPY
-
The present invention relates to derivatives of 5-alkyloxy-indolin-2-one, their method of production and their therapeutic applications. These novel derivatives have affinity and selectivity for the V2 receptors of vasopressin (“V2 receptors”) and can therefore constitute active principles of pharmaceutical compositions.
- -
-
Page/Page column 31-32
(2010/04/23)
-
- INDOLE DERIVATIVES USEFUL AS PPAR ACTIVATORS
-
There is provided according to the invention novel compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: (I) useful as PPAR activators.
- -
-
Page/Page column 89
(2009/05/30)
-
- Macrocyclic design strategies for small, stable parallel β-sheet scaffolds
-
(Figure Presented) Pairs of short peptide strands can be induced to adopt an antiparallel β-sheet secondary structure in aqueous solution via a macrocyclic constraint, as illustrated by many natural and designedpeptides. We show that an analogous strategy is successful for creation of small units of parallel β-sheet secondary structure in aqueous solution. Cyclization in this case requires nonpeptide segments for N-to -N and C-to-C interstrand linkage. Surprisingly, we find that only one of these segments needs to be preorganized.
- Freire, Felix,Gellman, Samuel H.
-
supporting information; experimental part
p. 7970 - 7972
(2009/12/02)
-
- N,N-Dichloroaminosulfonic acids as novel topical antimicrobial agents
-
2-Dichloroamino-2-methyl-propane-1-sulfonic acid sodium salt (2a), a stable derivative of endogenous N,N-dichlorotaurine (1), has been identified and is under development as a topical antimicrobial agent. Structure-activity relationships of analogs were explored to achieve optimal antimicrobial activity with minimal mammalian toxicity while maintaining the desired stability. All the analogs synthesized showed antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans in the range of 1-128 μg/mL and cytotoxicity against mammalian L929 cells in the range 80-1900 μg/mL.
- Low, Eddy,Nair, Satheesh,Shiau, Timothy,Belisle, Barbara,Debabov, Dmitri,Celeri, Chris,Zuck, Meghan,Najafi, Ron,Georgopapadakou, Nafsika,Jain, Rakesh
-
scheme or table
p. 196 - 198
(2009/05/07)
-
- METHOD FOR 1H-IMIDAZO[4,5-c]PYRIDINES AND ANALOGS THEREOF
-
Methods and intermediates for preparing compounds of the Formulas: (I and X) are disclosed. The methods include a method providing a compound of the Formula: (IV) and converting a compound of Formula IV to a compound of Formula I, a method providing a compound of the Formula: (VIII) and converting a compound of Formula VIII to a compound of Formula I, and a method providing a compound of the Formula: (XI) and converting a compound of Formula XI to a compound of Formula I.
- -
-
Page/Page column 83
(2008/06/13)
-
- Helical complexes containing diamide-bridged benzene-o-dithiolato/ catecholato ligands
-
The benzene-o-dithiol/catechol ligands H4-2 and H4-3 react with [TiO(acac)2] to give the dinuclear, double-stranded anionic complexes [Ti2(L)2(μ-OCH3) 2]2- ([22]2-, L = 24-; [23] 2-, L = 34-). NMR spectroscopic investigations reveal that the complex anion [Ti2(2)2(μ-OCH3) 2]2- is formed as a mixture of three of four possible isomers/pairs of enantiomers, whereas only one isomer of the complex anion [Ti2(3)2(μ-OCH3)2]2- is obtained. The crystal structure analysis of (PNP)2- [Ti 2(3)2(μ-OCH3)2] shows a parallel orientation of the ligand strands, whereas the structure determination for (AsPh4)2[Ti2(2)2(μ-OCH 3)2] does not yield conclusive results about the orientation of the ligand strands due the presence of different isomers in solution, the possible co-crystallisation of different isomers and severe disorder in the crystal. NMR spectroscopy shows that ligand H4-3 reacts at elevated temperature with [TiO(acac)2] to give the triple-stranded helicate (PNP)4 [Ti2(3)3] ((PNP)4[24]) as a mixture of two isomers, one with a parallel orientation of the ligand strands and one with an antiparallel orientation. Exclusively the triple-stranded helicates [Ti2(L)3] 4- ([25]4-, L = 14-; [26]2-, L = 44-) are formed in the reaction of ligands H4-1 and H 4-4 with [TiO-(acac)2]. The molecular structures of Na(PNP)3[Ti2(1)3]·CH 3OH·H2O·Et2O (Na(PNP) 3[25]·CH3OH·H2O·Et 2O) and Na1.5(PNP)6.5[Ti2(4) 3]2·3 DMF (Na1.5(PNP) 6.5[26]2·3DMF) reveal a parallel orientation of the ligand strands in both complexes, which is retained in solution. The sodium cations present in the crystal structures lead to two different kinds of aggregation in the solid state. Na-[25]-Na-[25]-Na polymeric chains are formed from compound Na-(PNP)3[25], with the sodium cations coordinated by the carbonyl groups of two ligand strands from two different [Ti 2(1)3]4- ions in addition to solvent molecules. In contrast to this, two [Ti2(4)3]4- ions are connected by a sodium cation that is coordinated by the three meta oxygen atoms of the catecholato groups of each complex tetraanion to form a central (NaO 6) octahedron in the anionic pentanuclear complex {[26]-Na-[26]} 7-.
- Isfort, Christian Schulze,Kreickmann, Thorsten,Pape, Tania,Froehlich, Roland,Hahn, F. Ekkehardt
-
p. 2344 - 2357
(2008/02/04)
-
- CARDIOTONIC COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST BETA-ADRENERGIC RECEPTORS AND PHOSPHODIESTERASE
-
The present invention provides compounds possessing inhibitory activity against ? adrenergic receptors and phosphodiesterase (PDE), including type 3 phosphodiesterase (PDE-3). The present invention further provides pharmaceutical compositions comprising s
- -
-
Page/Page column 47
(2010/11/08)
-
- CYANOFLUOROPYRROLIDINE DERIVATIVE
-
A cyanofluoropyrrolidine compound of Formula (I) or a pharmaceutically acceptable salt thereof or a hydrate thereof, which is useful as an agent for preventing or treating diseases or conditions capable of being improved by inhibition of dipeptidyl peptidase IV (DPPIV), diabetes mellitus, immune diseases and the like: [wherein A represents a hydrogen atom or a fluorine atom, R1 and R2 are as defined in the specification, X represents a single bond or a C1-3 alkylene group, and R3 represents a group represented by the formula: -N(R4)COR5, -N(R4)SO2R5, -NR4R6, -SO2R5, -SO2NR4R5, -OCONR4R5, -CH=CH-R7 or -C≡C-R7, or represents a heteroaryl group selected from a heteroaryl group which contains at least one oxygen and/or sulfur atom and which may further contain a nitrogen atom, and a 6-membered nitrogen-containing aromatic ring or a 9- to 11-membered condensed ring thereof (wherein the heteroaryl group may be substituted with one or more substituents selected from the substituent Y3 group)].
- -
-
Page/Page column 19
(2010/11/08)
-
- COMPOUND INHIBITING DIPEPTIDYL PEPTIDASE IV
-
The invention aims to provide a dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. The invention is directed to a compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R1 and R2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or -COOR5 whereupon R5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R1 and R2, together with a carbon atom to which they are bound, represent a 3- to 6-membered cycloalkyl group, R3 represents hydrogen or an optionally substituted C6-10 aryl group, R4 represents a hydrogen or a cyano group, D represents -CONR6-, -CO- or -NR6CO-, R6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents -(CH2)m- whereupon m is an integer of 1 to 3, -CH2OCH2-, or -SCH2-, n is an integer of 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.
- -
-
Page/Page column 11
(2010/02/14)
-
- Selective synthesis of carbamate protected polyamines using alkyl phenyl carbonates
-
Utilising alkyl phenyl carbonates, an economical, practical and versatile method for selective Boc, Cbz and Alloc protection of polyamines has been developed. This method allows Boc, Cbz and Alloc protection of primary amines in the presence of secondary amines by reaction of the polyamines with the alkyl phenyl carbonates. Also, this method allows mono carbamate protection of simple symmetrical aliphatic α,ω-alkanediamines in high yields with respect to the diamine. Finally, the method allows selective carbamate protection of a primary amine located on a primary carbon in the presence of a primary amine located on a secondary or a tertiary carbon in excellent yields.
- Pittelkow, Michael,Lewinsky, Rasmus,Christensen, Jorn Bolstad
-
p. 2195 - 2202
(2007/10/03)
-
- Pyrimido[5,4]-dipyrimidines, pharmaceuticals containing them, their use and processes for the preparation thereof
-
Pyrimido[5,4-d]pyrimidines of the general formula [Figure] which have an inhibitory effect on signal transduction mediated by tyrosine kinases, their use for the treatment of disorders, in particular of oncoses, and their preparation. Exemplary compounds are: 4-[(3-Chloro-4-fluorophenyl)amino]-6-[1-methyl-4-piperidinylamino]pyrimido[5,4-d]pyrimidine, and 4-[(3-Chloro-4-fluorophenyl)amino]-6-[trans-4-dimethyl-aminocycohexylamino]pyrimido[5,4-d]pyrimidine.
- -
-
-
- Syntheses of HIV-protease inhibitors having a peptide moiety which binds to GP120
-
Some HIV-protease inhibitor derivatives having an N- carbomethoxycarbonyl-prolyl-phenylalanine benzyl ester (CPF) moiety as a binding site to gp120 were designed and synthesized. Almost all the compounds bearing CPF on the phenoxyacetyl group showed protease-inhibitory activity. Compounds 25a and 25b, which have the CPF moiety at the ortho- and meta- positions of the phenoxyacetyl group, respectively, had anti-HIV activity, although the others showed only protease-inhibitory activity. These results suggest that 25b binds to gp120 and inhibits HIV protease.
- Asagarasu, Akira,Uchiyama, Taketo,Achiwa, Kazuo
-
p. 697 - 703
(2007/10/03)
-