- 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.
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p. 6534 - 6545
(2021/08/03)
-
- NOVEL TRITERPENE DERIVATIVES AS HIV INHIBITORS
-
The present invention relates to novel triterpene derivatives of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and ring are as defined herein. The invention also relates to novel triterpene derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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-
-
- Vinyl Sulfone-Based Inhibitors of Nonstructural Protein 2 Block the Replication of Venezuelan Equine Encephalitis Virus
-
Emerging infectious diseases like those caused by arboviruses such as Venezuelan equine encephalitis virus (VEEV) pose a serious threat to public health systems. Development of medical countermeasures against emerging infectious diseases are of utmost importance. In this work, an acrylate and vinyl sulfone-based chemical series was investigated as promising starting scaffolds against VEEV and as inhibitors of the cysteine protease domain of VEEV's nonstructural protein 2 (nsP2). Primary screen and dose response studies were performed to evaluate the potency and cytotoxicity of the compounds. The results provide structural insights into a new class of potent nonpeptidic covalent inhibitors of nsP2 cysteine protease represented by compound 11 (VEEV TrD, EC50= 2.4 μM (HeLa), 1.6 μM (Vero E6)). These results may facilitate the evolution of the compounds into selective and broad-spectrum anti-alphaviral drug leads.
- Zhang, Huaisheng,Harmon, Moeshia,Radoshitzky, Sheli R.,Soloveva, Veronica,Kane, Christopher D.,Duplantier, Allen J.,Ogungbe, Ifedayo Victor
-
p. 2139 - 2145
(2020/12/17)
-
- NOVEL POTASSIUM CHANNEL INHIBITORS
-
The present invention relates to novel compounds, pharmaceutical compositions comprising such compounds and their use for treating, alleviating or preventing diseases or disorders relating to the activity of potassium channels.
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-
Page/Page column 56
(2020/10/20)
-
- ANTIMICROBIAL COMPOUNDS AND METHODS
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The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
- -
-
Paragraph 00447
(2020/07/31)
-
- Discovery of a Potent, Selective, and Brain-Penetrant Small Molecule that Activates the Orphan Receptor GPR88 and Reduces Alcohol Intake
-
The orphan G-protein-coupled receptor GPR88 is highly expressed in the striatum. Studies using GPR88 knockout mice have suggested that the receptor is implicated in alcohol seeking and drinking behaviors. To date, the biological effects of GPR88 activatio
- Jin, Chunyang,Decker, Ann M.,Makhijani, Viren H.,Besheer, Joyce,Darcq, Emmanuel,Kieffer, Brigitte L.,Maitra, Rangan
-
p. 6748 - 6758
(2018/07/25)
-
- Cu(I)-catalyzed synthesis of dihydropyrimidin-4-ones toward the preparation of β- And β3-amino acid analogues
-
A copper(I)-catalyzed synthesis of substituted dihydropyrimidin-4-ones from propargyl amides via the formation of ketenimine intermediate has been successfully developed; the synthesis afforded good isolated yields (80-95%). The mild reaction conditions at room temperature allow the reaction to proceed to completion in a few hours without altering the stereochemistry. Further, by involving a variety of reactive nucleophiles, the obtained substituted dihydropyrimidin-4-ones were elegantly transformed into the corresponding β- and β3-amino acid analogues.
- Rajagopal, Basker,Chen, Ying-Yu,Chen, Chun-Chi,Liu, Xuan-Yu,Wang, Huei-Ren,Lin, Po-Chiao
-
p. 1254 - 1264
(2014/03/21)
-
- DEUTERATED 1-PIPERAZINO-3-PHENYL-INDANES FOR TREATMENT OF SCHIZOPHRENIA
-
The present invention relates to deuterated 1-piperazino-3- phenyl-indanes and salts thereof with activity at dopamine receptors D1 and D2 as well as the 5HT2 receptors in the central nervous system, to medicaments comprising such compounds as active ingredients, to the use of such compounds in the treatment of diseases in the central nervous system, and to methods of treatment comprising administration of such compounds.
- -
-
-
- Discovery of highly potent human deoxyuridine triphosphatase inhibitors based on the conformation restriction strategy
-
Human deoxyuridine triphosphatase (dUTPase) inhibition is a promising approach to enhance the efficacy of thymidylate synthase (TS) inhibitor based chemotherapy. In this study, we describe the discovery of a novel class of human dUTPase inhibitors based on the conformation restriction strategy. On the basis of the X-ray cocrystal structure of dUTPase and its inhibitor compound 7, we designed and synthesized two conformation restricted analogues, i.e., compounds 8 and 9. These compounds exhibited increased in vitro potency compared with the parent compound 7. Further structure-activity relationship (SAR) studies identified a compound 43 with the highest in vitro potency (IC50 = 39 nM, EC50 = 66 nM). Furthermore, compound 43 had a favorable oral PK profile and exhibited potent antitumor activity in combination with 5-fluorouracil (5-FU) in the MX-1 breast cancer xenograft model. These results suggested that a dUTPase inhibitor may have potential for clinical usage.
- Miyahara, Seiji,Miyakoshi, Hitoshi,Yokogawa, Tatsushi,Chong, Khoon Tee,Taguchi, Junko,Muto, Toshiharu,Endoh, Kanji,Yano, Wakako,Wakasa, Takeshi,Ueno, Hiroyuki,Takao, Yayoi,Fujioka, Akio,Hashimoto, Akihiro,Itou, Kenjirou,Yamamura, Keisuke,Nomura, Makoto,Nagasawa, Hideko,Shuto, Satoshi,Fukuoka, Masayoshi
-
experimental part
p. 5483 - 5496
(2012/08/28)
-
- Synthesis of α, β-unsaturated γ-amino esters with unprecedented high (E)-stereoselectivity and their conformational analysis in peptides
-
Mild, efficient and racemization-free synthesis of N-protected α, β-unsaturated γ-amino esters with unprecedented high E- stereoselectivity is described. This method is found to be compatible with Boc-, Fmoc- and other side chain protecting groups. The crystal conformations of the vinylogous γ-amino esters in monomers and in homo- and mixed dipeptides are studied. Further, the vinylogous homo-dipeptide showed a β-sheet conformation, while mixed α- and α,β-unsaturated γ-hybrid dipeptide adapted an irregular structure in single crystals.
- Mali, Sachitanand M.,Bandyopadhyay, Anupam,Jadhav, Sandip V.,Kumar, Mothukuri Ganesh,Gopi, Hosahudya N.
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p. 6566 - 6574
(2011/11/05)
-
- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
-
Compounds having antibacterial activity are disclosed. The compounds have the following structure (I) including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, Q5, R1, R2, R3, Z1 and Z2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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Page/Page column 75
(2011/04/26)
-
- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
-
Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): (Formula (I)), including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2, R3, Z1 and Z2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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-
Page/Page column 80
(2011/04/26)
-
- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
-
Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): (Formula (I)), including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2, R3, Z1 and Z2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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-
Page/Page column 77-78
(2011/04/26)
-
- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
-
Compounds having antibacterial activity are disclosed. The compounds have one of the following structures (I) or (II): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2, R3 and Z1 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
- -
-
Page/Page column 104-105
(2011/04/26)
-
- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
-
Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): (I) including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Ql, Q2, Rl, R2 and R3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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-
Page/Page column 66
(2010/04/28)
-
- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
-
Compounds having antibacterial activity are disclosed. The compounds have the following structure (I) or (II): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, Q3, R1, R2 and R3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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-
Page/Page column 110
(2010/12/17)
-
- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
-
Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): (I) including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2 and R3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
- -
-
Page/Page column 66
(2010/04/28)
-
- TREATMENT OF URINARY TRACT INFECTIONS WITH ANTIBACTERIAL AMINOGLYCOSIDE COMPOUNDS
-
A method for treating a urinary tract infection in a mammal in need thereof is disclosed, the method comprising administering to the mammal an effective amount of an antibacterial aminoglycoside compound.
- -
-
Page/Page column 193
(2010/12/17)
-
- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
-
Compounds of structure (I): having antibacterial activity are disclosed, including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, Q3, R8 and R9 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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-
Page/Page column 185
(2009/06/27)
-
- PURINE DERIVATIVES USEFUL AS PI3 KINASE INHIBITORS
-
This invention provides a compound which is a purine of formula (Ia) or (Ib): and the pharmaceutically acceptable salts thereof that are inhibitors of PI3K and a selective for the p110δ isoform, which is a class Ia PI3 kinase, over other class Ia PI3 kinases and over class Ib kinases. The compounds may be used to treat diseases and disorders arisi from abnormal cell growth, function or behaviour associated with PI3 kinase such as cance immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.
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-
Page/Page column 69-70
(2009/05/28)
-
- CYCLIC AMINE COMPOUND
-
The present invention provides an excellent antihypertensive medicament. The medicament of the present invention comprises a compound having the general formula (I) and the like: [wherein R1: H, substitutable alkyl, substitutable alkenyl, substitutable cyclic hydrocarbon, substitutable heterocyclyl or the like; R2: H, substitutable alkyl, substitutable alkenyl, substitutable cycloalkyl or the like; R3, R4; H, substitutable alkyl, substitutable alkenyl, substitutable cycloalkyl or the like; R5, R6: H, substitutable alkyl, substitutable cycloalkyl, substitutable alkoxy or the like; R7, R8: H, substitutable alkyl, substitutable cycloalkyl or the like; X: the formula (II) or the like; A: substitutable cyclic hydrocarbon, substitutable heterocyclyl or the like; Y: a single bond, substitutable alkylene, substitutable alkenylene, -(CH2)a-X1-(CH2)b- (X1: the formula -NH-, -O- or the like; a, b: 0-5) or the like; B: substitutable cyclic hydrocarbon, substitutable heterocyclyl or the like].
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Page/Page column 149
(2009/04/23)
-
- ALPHA KETOAMIDE COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
-
The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 61
(2008/06/13)
-
- ALPHA KETOAMIDE COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
-
The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 71-72
(2010/11/24)
-
- ACETYLENE DERIVATIVES AS INHIBITORS OF HISTONE DEACETYLASE
-
The present invention is directed to certain hydroxamate derivatives that are inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.
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Page/Page column 52
(2010/02/11)
-
- HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
-
The application is directed to haloalkyl-substituted compounds of Formula (I), wherein R1, R1a, R2, R3, R4’ and E are as defined in the claims. The compounds are inhibitors of cysteine proteases, in p
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-
Page/Page column 51-52
(2010/02/11)
-
- AMIDINO COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
-
The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceu
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Page/Page column 49-50
(2010/02/09)
-
- Pyrrolotriazinone compounds and their use to teat diseases
-
The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof useful for inducing mitotic arrest thereby making them useful as anti-cancer agents and other diseases which can be treated by inducing mitotic arrest.
- -
-
-
- PYRROLOTRIAZINONE COMPOUNDS AND THEIR USE TO TREAT DISEASES
-
The present invention provides compounds of Formula (I), and pharmaceutically acceptable salts thereof useful for inducing mitotic arrest thereby making them useful as anti-cancer agents and other diseases which can be treated by inducing mitotic arrest.
- -
-
-
- PEPTIDIC COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
-
The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
- -
-
-
- Compounds with growth hormone releasing properties
-
The present invention relates to compounds, compositions containing them, and their use for treating medical disorders resulting from a deficiency in growth hormone.
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-
Page column 36-37
(2010/02/06)
-
- Substituted bicyclic derivatives useful as anticancer agents
-
The invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts and solvates thereof, wherein A, X, R1, R3and R4are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals with administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.
- -
-
-
- Morpholinones as light stabilizers
-
The invention relates to new compounds containing 1-8 active groups of the type 3,3,6,6-polysubstituted 2-morpholinone and having the formula F(A'-Z)m-X(F),wherein m is a number from 1 to 8; X is an organic anchor group of valency m and in case that m is not 1, X may also be a direct bond, SO2, P or PO; A' is a monovalent group of the formula E containing one linking group; Z is a direct bond, -O-, -S-, -SO-, -SO2- or -NR'14-; provided that Z is -O-, -S-, -SO-, -SO2- or -NR'14- if m is 1 and the linking group in formula E is G3 or G5; G1 is hydrogen; C1-C18alkyl; C2-C18alkyl substituted by OH and/or phenyl; oxyl; OH; C2-C12cyanoalkyl; C2-C12cyanoalkoxy; C1-C18alkoxy; C5-C12cycloalkoxy; C3-C8alkenyl; C3-C8alkynyl; C3-C8alkenyloxy; C7-C12phenylalkyl; C7-C12phenylalkyl substituted by hydroxy, C1-C4alkyl and/or C1-C4alkoxy; C7-C15phenylalkoxy; C7-C15phenylalkoxy, which is substituted by C1-C4alkyl and/or C1-C4alkoxy; or G1 is C1-C8alkanoyl; C3-C5alkenoyl; C1-C18alkanoyloxy; C3-C8epoxyalkyl; or G1 is the linking group -R10-; G2 and G4 are, independently of one another, C1-C18alkyl, C5-C12cycloalkenyl, C5-C12cycloalkyl, or an oligocyclic hydrocarbon residue of 6-12 carbon atoms; G3 is as defined for G2 or is C1-C8hydroxyalkyl; or G2 and G3 together are (CH2)e, where e is a number from 4 to 11; or G5 is the linking group -R5-; G5 is as defined for G4 or is C1-C8hydroxyalkyl; or G4 and G5 together are (CH2)e, where e is number from 4 to 11; or G5 is the linking group -R5-; G6 is as defined for G4 or is hydrogen; or G6 is the linking group, which is a direct bond or -R5-; and other residues are as defined in claim 1. The new compounds are effective as stabilizers for organic material, especially coatings, against harmful effects of light, oxygen and/or heat.
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-
-
- Compounds with growth hormone releasing properties
-
There are disclosed novel synthetic peptides of formula (I) where A, B, D, E, F, G, J, m, n, and p are defined in the specification. Compounds of formula (I) promote the release of growth hormone in humans and animals. Growth promoting compositions containing such compounds of formula (I) as the active ingredient, methods of stimulating the release of growth hormone, and the use of such compounds of formula (I) are also disclosed.
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-
-
- Benzolactam growth hormone secretagogues: Replacement of the C-3 amide bond in L-692,429
-
The synthesis and structure-activity relationships of various C-3 amide bond modifications in the novel nonpeptidyl growth hormone secretagogue L-692,429 are described. Several C-3 amide surrogates were prepared and the urea moiety was found to exhibit growth hormone releasing activity similar to that observed with L-692,429.
- Ok, Hyun O.,Szumiloski, John L.,Doldouras, George A.,Schoen, William R.,Cheng, Kang,Chan, Wanda W.-S.,Butler, Bridget S.,Smith, Roy G.,Fisher, Michael H.,Wyvratt, Matthew J.
-
p. 3051 - 3056
(2007/10/03)
-
- Studies on agents with vasodilator and β-blocking activities. IV
-
A series of novel pyridazinone derivatives (II) having a phenoxypropanolamine moiety was synthesized. Their hypotensive and β- blocking activities were evaluated after intravenous administration of the compounds to anesthetized rats. Among them, the 5-chloro-2-cyanophenoxy derivative (29) showed the promising dual activities and was selected for further studies.
- Seki, Toshimi,Nakao, Tomio,Masuda, Takeshi,Hasumi, Kohichi,Gotanda, Kotaro,Ishimori, Tsutomu,Honma, Seijiro,Minami, Nobuyoshi,Shibata, Kenyu,Yasuda, Kikuo
-
p. 2061 - 2069
(2007/10/03)
-
- Furan-, pyrrole-, and thiophene-based siloxydienes for syntheses of densely functionalized homochiral compounds
-
This review describes the methods of preparation and use of 2-(trimethylsiloxy)furan, N-(tert-butoxycarbonyl)-2-(tert-butyldimethylsiloxy)pyrrole, and certain substituted analogues and congeners, including novel 2-(tert-butyldimethylsiloxy)thiophene, to synthesize complex carbohydrates, azasugars, polyhydroxylated alkaloids, C-glycosylated α-amino acids, amino acids bearing quaternary chiral carbon atoms, and thiosugars. Especially emphasized is the preparation of enantiomerically pure compounds of biological interest. Some mechanistic insights are presented.
- Casiraghi,Rassu
-
p. 607 - 626
(2007/10/02)
-
- Reagents, methods and kits for an amphetamine-class fluorescence polarization immunoassay
-
A fluorescence polarization immunoassay (FPIA) for detecting the presence of one or more amphetamine-class analytes in a test sample is provided. The immunoassay uses competition between the analyte and a fluorescently labeled tracer for the binding site
- -
-
-
- Antihypertensive pyridazinone aminoisopropanol derivatives
-
A pyridazinone derivative represented by the following general formula STR1 wherein R1 represents a hydrogen atom or a methyl group, either one of R2, R3 and R4 represents a hydrogen atom and the remaining two of them represent a lower alkyl group, a trifluoromethyl group, a halogen atom, a cyano group or a nitro group, and a salt thereof. The compounds are useful as antihypertensive agents.
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