- EIF4E INHIBITORS AND USES THEREOF
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The present invention provides compounds inhibiting elF4E activity and compositions and methods of using thereof.
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Paragraph 00506; 00521
(2021/09/11)
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- Aromatic β-sheet foldamers based on tertiary squaramides
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The preference of N,N-aryl, alkyl tertiary amides for cis conformations has been exploited through the use of tertiary squaramides as hairpin turn units that promote the folding of aromatic β-sheets. Head-to-head aromatic arrangements were shown to prevail in sufficiently long bent aromatic sequences.
- Atcher, Joan,Nagai, Aki,Mayer, Peter,Maurizot, Victor,Tanatani, Aya,Huc, Ivan
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supporting information
p. 10392 - 10395
(2019/09/07)
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- Folding and Assembly of Short α, β, ?-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures
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Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of α-, β-, and aromatic ?-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, 1 and 2a or 2b, differing only in their central αβ hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer 1 folds into an expanded β-turn containing an unusual hybrid α/β-amino acid sequence composed of glycine and β-alanine, two α- A nd β-amino acid residues that are conformationally most flexible, and peptides 2a and 2b adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, αβ vs βα, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of 1 and 2. The revealed turn and double helix have few natural or synthetic counterparts, and provide novel and unique folding prototypes based on which chiral α- A nd β-amino acids are incorporated. The resultant derivatives 1a, 1b, 2c, and 2d follow the same folding and assembling behavior and demonstrate the generality of this system with the formation of expanded β-turns and double helices with enhanced folding stabilities, hampered helix inversion, as well as defined and dominant helical sense. This work has demonstrated the unique capability of synthetic foldamers in generating structures with fascinating folding and assembling behavior. The revealed systems offer ample opportunity for further structural optimization and applications.
- Zhang, Yukun,Zhong, Yulong,Connor, Alan L.,Miller, Daniel P.,Cao, Ruikai,Shen, Jie,Song, Bo,Baker, Erin S.,Tang, Quan,Pulavarti, Surya V.S.R.K.,Liu, Rui,Wang, Qiwei,Lu, Zhong-Lin,Szyperski, Thomas,Zeng, Huaqiang,Li, Xiaopeng,Smith, Richard D.,Zurek, Eva,Zhu, Jin,Gong, Bing
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supporting information
p. 14239 - 14248
(2019/10/11)
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- NOVEL COMPOUNDS FOR USE IN CANCER
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It relates to the compounds of formula (I), or their pharmaceutically or veterinary acceptable salts, or their stereoisomers or mixtures of stereoisomers, wherein X, L,R1, R 2, and R 3 are as defined herein, which are cancer cell differentiation inducing agents. It also relates to pharmaceutical or veterinary compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of cancer, in particular by cell differentiation therapy.
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Page/Page column 77
(2019/01/07)
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- One-Pot C?H Functionalization of Arenes by Diaryliodonium Salts
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A transition-metal-free, mild, and highly regioselective synthesis of nitroarenes from arenes has been developed. The products are obtained in a sequential one-pot reaction by nitration of iodine(III) reagents with two carbon ligands, which are formed in situ from iodine(I). This novel concept has been extended to formation of aryl azides, and constitutes an important step towards catalytic reactions with these hypervalent iodine reagents. An efficient nitration of isolated diaryliodonium salts has also been developed, and the mechanism is proposed to proceed by a [2,2] ligand coupling pathway.
- Reitti, Marcus,Villo, Piret,Olofsson, Berit
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p. 8928 - 8932
(2016/07/26)
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- Compounds for use in treatment of mucostitis
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The present invention provides methods for treating and/or preventing mucostitis with one or more compounds, or pharmaceutically acceptable salts thereof, disclosed herein, or compositions comprising the same.
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Page/Page column 377
(2015/11/09)
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- NOVEL 4,6-DISUBSTITUTED AMINOPYRIMIDINE DERIVATIVES HAVING BOTH AROMATIC AND HALOGENIC SUBSTITUENTS
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Certain 4,6-disubstituted aminopyrimidine derivatives having both aromatic and halogenic substituents.
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Paragraph 0280; 0281
(2014/03/24)
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- Control over unfolding pathways by localizing photoisomerization events within heterosequence oligoazobenzene foldamers
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From the inside out or from the outside in? Two photoswitchable foldamers that incorporate azobenzene moieties as the energy-acceptor units have been designed. The pathway of helix unfolding can be controlled by localizing these photoinduced triggers (sho
- Yu, Zhilin,Hecht, Stefan
-
supporting information
p. 13740 - 13744
(2014/01/06)
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- TRIAZOLONE COMPOUNDS AS mPGES-1 INHIBITORS
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The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.
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- Design and Synthesis of Novel Cyclooxygenase-1 Inhibitors as Analgesics: 5-Amino-2-ethoxy-N-(substituted-phenyl)benzamides
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We previously found that N-(4-aminophenyl)-4-trifluoromethylbenzamide (TFAP), a COX-1 inhibitor, exhibits an analgesic effect without causing gastric damage. Unfortunately, TFAP causes reddish purple coloration of urine, and its analgesic effect is less potent than that of indomethacin. Herein we describe our study focusing on the development of 4- and 5-amino-2-alkoxy-N-phenylbenzamide scaffolds, designed on the basis of the structures of TFAP and parsalmide, another known COX-1 inhibitory analgesic agent. 5-Amino-2-ethoxy-N-(2- or 3-substituted phenyl)benzamide derivatives exhibited analgesic activity in a murine acetic acid induced writhing test. Among these compounds, 5-amino-2-ethoxy-N-(2-methoxyphenyl)benzamide (9v) possesses potent COX-1 inhibitory and analgesic activities, similar to those of indomethacin. In addition, 5-amino-2-ethoxy-N-(3-trifluoromethylphenyl)benzamide (9g) showed a more potent analgesic effect than indomethacin or 9v without causing apparent gastric damage or coloration of urine, although its COX-1 inhibitory activity was weaker than that of indomethacin or 9v. Thus, 9g and 9v appear to be promising candidates for analgesic agents and are attractive lead compounds for further development of COX-1 inhibitors.
- Fukai, Ryosuke,Zheng, Xiaoxia,Motoshima, Kazunori,Tai, Akihiro,Yazama, Futoshi,Kakuta, Hiroki
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p. 550 - 560
(2011/12/22)
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- Mizoroki-heck reactions with 4-phenoldiazonium salts
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Significantly better yields were achieved in Mizoroki-Heck reactions using 4-phenoldiazonium salts instead of their O-alkylated analogues under otherwise identical conditions. We found that a one-flask deacetylation-diazotation- precipitation sequence starting from paracetamol or acetanilides derived thereof provides a convenient access to the required diazonium tetrafluoroborates. The utility of these arylating agents in palladium-catalyzed C-C bond forming reactions was demonstrated for a one-flask-synthesis of the heterocyclic core of the drug aripiprazole. Notably, the diazonium salt formation from an acetanilide could be combined with two Pd-catalyzed steps in a one-flask sequence, without any exchange of solvents or isolation of intermediates.
- Schmidt, Bernd,Hoelter, Frank,Berger, Rene,Jessel, Soenke
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supporting information; experimental part
p. 2463 - 2473
(2010/12/25)
-
- Anion binding of N-(o-Methoxybenzamido)thioureas: Contribution of the intramolecular hydrogen bond in the N-benzamide moiety
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N-(o-Methoxybenzamido)- thioureas (2X/2Y) are found to show an enhanced anion binding affinity with binding constants over 107 mol -1L orders of magnitude for AcO- and a redshifted absorption of the anion binding complexes in acetonitrile (MeCN) relative to those of N-benzamidothioureas (1) that bear no o- OMe in the N-benzamide moiety, despite the electron-donating character of o-OMe. Absorption of the anion-2X/ 2Y complex was shown to be of the same charge-transfer nature as that of the anion-1 complex, but its dependence on substituent X is interestingly influenced by the o-MeO···HNC=O six-membered-ring intramolecular hydrogen bond identified in 2X/2Y. Such an intramolecular hydrogen bond is suggested to be responsible for the enhanced anion binding affinity. In the presence of this intramolecular hydrogen bond, the anion binding constant of 2X was found to be independent of substituent X at the N-phenyl ring, as in the case of 1, whereas that of 2Y showed an amplified dependence on substituent Y at the N′-phenyl ring, but to a lower extent than that of 1. A similar ring intramolecular hydrogen bond was purported to exist in 2Za, 2Zd, and 2Ze, which bear NHMe, F, and Cl as the ortho substituent in the N-benzamide moiety. In terms of the current roles of thiourea in not only anion recognition and sensing but also organocatalysis and crystal engineering, the present finding would be of significance for a wider structural diversity of smart thiourea derivatives with predesigned functions.
- Jiang, Qian-Qian,Darhkijav, Burenkhangai,Liu, Hao,Wang, Fang,Li, Zhao,Jiang, Yun-Bao
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experimental part
p. 543 - 549
(2010/08/20)
-
- Discovery of novel non-peptide inhibitors of BACE-1 using virtual high-throughput screening
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A novel series of isatin-based inhibitors of β-secretase (BACE-1) have been identified using a virtual high-throughput screening approach. Structure-activity relationship studies revealed structural features important for inhibition. Docking studies suggest these inhibitors may bind within the BACE-1 active site through H-bonding interactions involving the catalytic aspartate residues.
- Yi Mok,Chadwick, James,Kellett, Katherine A.B.,Hooper, Nigel M.,Johnson, A. Peter,Fishwick, Colin W.G.
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scheme or table
p. 6770 - 6774
(2010/06/12)
-
- Strategic studies in the syntheses of novel 6,7-substituted quinolones and 7- or 6-substituted 1,6- and 1,7-naphthyridones
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This paper describes the different strategies devised and applied to overcome the selectivity issues in the syntheses of 6,7-disubstituted-1H-quinolin-4-one, 7-substituted-1H-1,6-naphthyridin-4-one and 6-substituted-1H-1,7-naphthyridin-4-one derivatives. They allowed us to improve the overall yields and the scaling-up feasibility. Several examples illustrate these strategies with their advantages and drawbacks.
- Morgentin, Rémy,Pasquet, Georges,Boutron, Pascal,Jung, Frédéric,Lamorlette, Maryannick,Maudet, Micka?l,Plé, Patrick
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p. 2772 - 2782
(2008/09/19)
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- Further studies on hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors toward improved replicon cell activities: Benzimidazole and structurally related compounds bearing the 2-morpholinophenyl moiety
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Following the discovery of JTK-109 (1) as a potent inhibitor of hepatitis C virus NS5B RNA-dependent RNA polymerase, [(a) Hirashima, S.; Suzuki, T.; Ishida, T.; Noji, S.; Yata, S.; Ando, I.; Komatsu, M.; Ikeda, S.; Hashimoto, H. J. Med. Chem. 2006, 49, 4721. (b) Hashimoto, H.; Mizutani, K.; Yoshida, A. Int. Patent Appl. WO 01/47883, 2001.] further studies toward the improvement of the cellular potency have been performed. A greater than 40-fold improvement was achieved through replacing the biphenyl moiety with a 2-morpholinophenyl group and the benzimidazole ring with the tetracyclic scaffold to afford compound 7 with an excellent replicon potency (EC50 = 7.6 nM).
- Hirashima, Shintaro,Oka, Takahiro,Ikegashira, Kazutaka,Noji, Satoru,Yamanaka, Hiroshi,Hara, Yoshinori,Goto, Hiroyuki,Mizojiri, Ryo,Niwa, Yasushi,Noguchi, Toru,Ando, Izuru,Ikeda, Satoru,Hashimoto, Hiromasa
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p. 3181 - 3186
(2008/02/07)
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- 1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists. Structure-activity relationships of 6-substituted and 5,6-disubstituted benzoic acid derivatives
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Herein we describe the SAR of 1,5-biaryl pyrrole derivatives, with substituents in the 6-position of the benzoic acid moiety, as EP1 receptor antagonists. Substitution at this position was well tolerated and led to the identification of several analogues with high affinity for the EP1 receptor that displayed good efficacy in the established FCA model of inflammatory pain. Furthermore, several analogues were prepared which combined substitution at the 5- and 6-positions as well as derivatives with an aromatic ring fused to the 5- and 6-positions.
- Hall, Adrian,Brown, Susan H.,Chessell, Iain P.,Chowdhury, Anita,Clayton, Nicholas M.,Coleman, Tanya,Giblin, Gerard M.P.,Hammond, Beverley,Healy, Mark P.,Johnson, Matthew R.,Metcalf, Ann,Michel, Anton D.,Naylor, Alan,Novelli, Riccardo,Spalding, David J.,Sweeting, Jennifer,Winyard, Lisa
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p. 916 - 920
(2007/10/03)
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- Prototype of a photoswitchable foldamer
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(Figure Presented) Know where to fold 'em: A foldamer exhibiting a light-induced helix-coil transition (see scheme) can be constructed by introducing a photochromic azobenzene moiety (red) into the center of an amphiphilic phenylene ethynylene backbone (blue). This system gives insight into folding and unfolding mechanisms and promises applications in photoresponsive (bio)materials and "smart" delivery devices based on photoresponsive dynamic receptors.
- Khan, Anzar,Kaiser, Christian,Hecht, Stefan
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p. 1878 - 1881
(2007/10/03)
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- POLYCATIONIC COMPOUNDS AND USES THEREOF
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Aspects of the present invention relate to compounds and methods useful in modulating angiogenesis and methods of treating or preventing diseases associated with angiogenesis by administering a polycationic compound. The present invention relates to metho
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Page/Page column 27
(2008/06/13)
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- SUBSTITUTED 4-(1H-BENZIMIDAZOL-2-YL)[1,4]DIAZEPANES USEFUL FOR THE TREATMENT ALLERGIC DISEASES
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The present invention relates to novel 4-(1H-benzimidazol-2-yl)[1,4] diazepane derivatives of formula (1): and stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- NOVEL HETEROCYCLIC SUBSTITUTED PYRROLIDINE AMIDE DERIVATIVES
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The present invention relates to novel heterocyclic substituted pyrrolidine amide derivatives of formula (1), and stereoisomers and pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, cough, and bronchitis.
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- AMINOMETHYLENE SUBSTITUTED NON-AROMATIC HETEROCYCLES AND USE AS SUBSTANCE P ANTAGONISTS
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The present invention relates to novel aminomethylene substituted non-aromatic heterocycles and, specifically, to compounds of the formula wherein W, R 1, R 2, R 3, A, X', Y' and Z' are as defined in the specification, and to intermediates used in the synthesis of such compounds. The novel compounds of formulae Ia and Ib are useful in the treatment of inflammatory and central nervous system disorders, as well as other disorders.
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- Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic disease
-
The present invention relates to novel 4-(1H-benzimidazol-2-yl)[1,4]diazepane derivatives of formula (1): and stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- Novel substituted 4-(1H-benzimidazol-2-yl) [1,4]diazepanes useful for the treatment of allergic diseases
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The present invention relates to novel 4-(1H-benzimidazol-2-yl)[1,4]diazepane derivatives of formula and stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- Substituted 4-(1H-benzimidazol-2-yl-amino)piperidines useful for the treatment of allergic diseases
-
The present invention relates to novel substituted piperidine derivatives of formula (1), stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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-
- Carboxy substituted acylic carboxamide derivatives
-
The present invention relates to novel carboxy substituted acyclic carboxamide derivatives of formula (1)): STR1and stereoisomers and pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, cough, and bronchitis.
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-
- CARBOXYSUBSTITUTED CYCLIC CARBOXAMIDE DERIVATIVES
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The present invention relates to novel carboxy substituted cyclic carboxamide derivatives of formula (1), STR1 and stereoisomers and pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, coughs and bronchitis.
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- SUBSTITUTED N-METHYL-N-(4-(PIPERIDIN-1-YL)-2-(ARYL)BUTYL)BENZAMIDES USEFUL FOR THE TREATMENT OF ALLERGIC DISEASES
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The present invention relates to novel substituted N-methyl-N-(4-(piperidin-1-yl)-2-(aryl)butyl)benzamide derivatives of the formula STR1 stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- SUBSTITUTED N-METHYL-N-(4-(4-(1H-BENZIMIDAZOL-2-YL) {1,4}DIAZEPAN-1-YL)-2-(ARYL)BUTYL) BENZAMIDES USEFUL FOR THE TREATMENT OF ALLERGIC DISEASES
-
The present invention relates to novel N-methyl-N-(4-(4-(1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)-2-(aryl)butyl)benzamide derivatives of the formula: STR1 stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- SUBSTITUTED N-METHYL-N-(4-(4-(1H-BENZIMIDAZOL-2-YL-AMINO) PIPERIDIN-1-YL)-2-(ARLYL) BUTYL) BENZAMIDES USEFUL FOR THE TREATMENT OF ALLERGIC DISEASES
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The present invention relates to novel substituted N-methyl-N-(4-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)-2-(aryl)butyl) benzamide derivatives of the formula: STR1 stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.
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- N-phenyl-N-acetamidoglycinamides, their preparation and medicaments containing them
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Compounds of formula: STR1 in which R1 represents a hydrogen atom or an alkyl, alkoxycarbonyl or an unsubstituted or substituted phenyl radical, R2 represents a hydrogen atom or an unsubstituted or substituted alkyl radical, R3 represents an alkyl, phenylalkyl, indanyl, cycloalkylalkyl or an unsubstituted or substituted phenyl radical, or R2 and R3 form a heterocycle together with the nitrogen atom to which they are attached, and R4 represents an unsubstituted or substituted phenyl radical, a naphthyl, indolyl or quinolyl radical or a phenylamino radical in which the phenyl ring is unsubstituted or substituted, their preparation and medicaments containing them.
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-
- (S)-N--5-iodo-2-methoxybenzamide Hydrochloride, a New Selective Radioligand for Dopamine D-2 Receptors
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From salicylic acid, the two enantiomers of N--5-iodo-2-methoxybenzamide (6b) were prepared in a five-step synthesis.With use of Heindel's triazene method for introduction of the radionuclide, the iodine-125-labeled substit
- Paulis, Tomas de,Janowsky, Aaron,Kessler, Robert M.,Clanton, Jeffrey A.,Smith, Howard E.
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p. 2027 - 2033
(2007/10/02)
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- Structures of ent-Herbertane Sesquiterpenoids displaying Antifungal Properties from the Liverwort Herberta adunca
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Several aromatic sesquiterpenoids displaying antifungal propaerties have been isolated from the liverwort Herberta adunca together with a mother hydrocarbon with a novel irregular sesquiterpene skeleton, ent-herbertane, and their structures and absolute configurations have been determined on the basis of extensive degradation reactions and spectroscopic evidence.The biological activity is also described.
- Matsua, Akihiko,Yuki, Shunji,Nakayama, Mitsuru
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p. 701 - 710
(2007/10/02)
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- Synthesis and Neuroleptic Activity of N--2-methoxy-5-sulfonamidobenzamides
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A series of some novel N-benzamides involving replacement of the sulfamoyl group in sulpiride with a sulfonamido group was synthesized and tested for dopamine receptor blockade.In comparison with sulpiride, several compounds were considerably more potent than sulpiride as dopamine receptor blockers.The structure-activity relationships are discussed.
- Ogata, Masaru,Matsumoto, Hiroshi,Kida, Shiro,Shiomi, Teruo,Eigyo, Masami,Hirose, Katsumi
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p. 1137 - 1141
(2007/10/02)
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