- MELANOCORTIN-4 RECEPTOR AGONISTS
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The present invention relates to a compound exhibiting excellent agonist activity against melanocortin receptors. More specifically, the present invention relates to a compound of Formula 1, a pharmaceutical composition comprising the compound as an activ
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Paragraph 91-94
(2021/05/15)
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- PROLINE-BASED NEUROPEPTIDE FF RECEPTOR MODULATORS
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Neuropeptide FF receptor modulators based on a proline scaffold are provided which offer NPFF receptor potencies in the nanomolar range and antagonistic selectivity for the NPFF 1 receptor. Methods, compounds and compositions for modulating the function o
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Paragraph 000216
(2018/09/18)
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- Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life
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Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 ± 0.03 to 1.35 ± 0.21 μM with the peptide γTatM4) and Gram-negative (MICs 0.71 ± 0.005 to 1.26 ± 0.02 μM with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid. The introduction of the non-natural amino acids of the study in the Tat peptide analogues results in increased resistance to degradation by proteolysis, significantly increasing their half-life. The peptides appear to inhibit bacteria by a membrane disruption mechanism, and have only a low cytotoxic effect on mammalian cells.
- Bhosle, Govind S.,Nawale, Laxman,Yeware, Amar M.,Sarkar, Dhiman,Fernandes, Moneesha
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supporting information
p. 358 - 369
(2018/05/22)
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- Superior HIV-1 TAR Binders with Conformationally Constrained R52 Arginine Mimics in the Tat(48–57) Peptide
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We report a 100-fold increase in binding affinity of the Tat(48–57) peptide to HIV-1 transcriptional activator-responsive element (TAR) RNA by replacing Arg52, an essential and critical residue for Tat's specific binding, with (2S,4S)-4-guanidinoproline. The resulting αTat1M peptide is a far superior binder than γTat1M, a peptide containing another conformationally constrained arginine mimic, (2S,4S)-4-amino-N-(3-guanidinopropyl)proline, or even the control Tat peptide (CtrlTat) itself. Our observations are supported by circular dichroism (CD), isothermal titration calorimetry (ITC), gel electrophoresis and UV spectroscopy studies. Molecular dynamics simulations suggest increased interactions between the more compact αTat1M and TAR RNA, relative to CtrlTat. The CD signature of the RNA itself remains largely unchanged upon binding of the peptides. The Tat mimetics further have better cell uptake properties than the control Tat peptide, thus increasing their potential application as specific TAR-binding molecules.
- Bhosle, Govind S.,Kharche, Shalmali,Kumar, Santosh,Sengupta, Durba,Maiti, Souvik,Fernandes, Moneesha
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supporting information
p. 220 - 226
(2018/01/22)
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- An ionic liquid containing L-proline moiety as highly efficient and recyclable chiral organocatalyst for Michael addition
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A novel chiral ionic liquid containing proline moiety was synthesized. It can be used as a highly efficient and recyclable chiral organocatalyst for Michael addition of cyclohexanone with (E)-β-nitroalkenes in methanol at room temperature. The Michael add
- Li, Jiang,Li, Xia Bing,Ma, Sha Sha,Liu, Juan,Li, Ben Hao,Li, Bao Lin
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p. 1259 - 1264
(2016/08/12)
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- Discovery of a series of novel compounds with moderate anti-hepatitis C virus NS3 protease activity in vitro
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The hepatitis C virus (HCV) NS3/4A protease that plays an important role in the viral life cycle has been proven to be an excellent target for the discovery of anti-HCV drugs. Enlightened by some P2-triazole and amide compounds, which had been found as HCV NS3 protease inhibitors, we designed and synthesized a series of novel compounds by incorporating different amino acid residues in P1/P1′ and P3/P3′ position to develop novel antiviral agents. The result of enzyme inhibition assay indicated that all the designed compounds showed moderate anti-HCV NS3 protease activity. On the basis of the biological result, a detailed structure-activity relationship (SAR) was derived and discussed.
- Shi, Fangyuan,Zhang, Yingjie,Xu, Wenfang
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p. 5539 - 5545
(2015/11/11)
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- Exploration of labeling by near infrared dyes of the polyproline linker for bivalent-type CXCR4 ligands
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We have previously used poly-l-proline linkers for the development of bivalent-type ligands for the chemokine receptor, CXCR4. The bivalent ligands with optimum linkers showed specific binding to CXCR4, suggesting the existence of CXCR4 possibly as a dime
- Nomura, Wataru,Aikawa, Haruo,Taketomi, Shohei,Tanabe, Miho,Mizuguchi, Takaaki,Tamamura, Hirokazu
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p. 6967 - 6973
(2015/11/11)
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- AZAQUINAZOLINE INHIBITORS OF ATYPICAL PROTEIN KINASE C
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The present invention provides a compound of formula (I) or a salt thereof, wherein R7, R8, R9, G, and X are as defined herein. A compound of formula (I) and its salts have a PKC inhibitory activity, and may be used to treat proliferative disorders.
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Page/Page column 223-224
(2014/04/17)
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- HEPATITIS C VIRUS INHIBITORS
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The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
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Paragraph 0326
(2013/05/21)
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- Remarkable structure effects on chiroptical properties of polyisocyanides carrying proline pendants
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Chiral polymers with simple chemical structures and high helical conformation stabilities are important for their applications as chiral supports and asymmetrical catalysts. We report herein the synthesis of a series of aliphatic polyisocyanides carrying proline pendants of different chiralities, and an investigation of the effects of the chemical structures of these pendants on the chiroptical properties of the polymers. The configuration of the chiral center at the 4-position of the proline pendants was changed from S to R to check its effect on the handedness of the helical conformation. To examine the effects of steric hindrance on the stabilities of the helical conformation for these aliphatic representatives, proline pendants with various substituents at both the carboxyl and amine terminals were designed. To further examine the steric effects of the proline pendants, aromatic counterparts were also prepared. In the latter case, the effects of hydrogen bonds between pendant units on the enhancement and stabilities of the helical conformation were investigated by switching from the ester to an amide linkage. The Cotton effects and signal intensities of both aliphatic and aromatic polyisocyanides from circular dichroism spectroscopy were compared based on the bulkiness of the pendant groups, solvent polarities, and solution temperatures. It was found that highly stable helical conformations of polyisocyanides could be imposed by small bulky monoproline pendants. Twisted sisters: Polyisocyanides with various proline-based pendant groups were synthesized and their chiroptical properties investigated. These chiral polymers show unprecedented stable helical conformations in different solvents at various temperatures, even in the absence of strong hydrogen-bonding interactions between the pendant groups (see picture). Copyright
- Xu, Anqiu,Hu, Guixia,Hu, Yulong,Zhang, Xiuqiang,Liu, Kun,Kuang, Guichao,Zhang, Afang
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p. 2003 - 2014
(2013/09/23)
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- Synthesis of deoxynucleoside triphosphates that include proline, urea, or sulfonamide groups and their polymerase incorporation into DNA
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To expand the chemical array available for DNA sequences in the context of in vitro selection, I present herein the synthesis of five nucleoside triphosphate analogues containing side chains capable of organocatalysis. The synthesis involved the coupling
- Hollenstein, Marcel
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supporting information
p. 13320 - 13330,11
(2012/12/12)
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- Synthesis of deoxynucleoside triphosphates that include proline, urea, or sulfonamide groups and their polymerase incorporation into DNA
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To expand the chemical array available for DNA sequences in the context of in vitro selection, I present herein the synthesis of five nucleoside triphosphate analogues containing side chains capable of organocatalysis. The synthesis involved the coupling
- Hollenstein, Marcel
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supporting information
p. 13320 - 13330
(2013/01/15)
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- Synthesis of chiral pyrrolidine isostere inserted into pyrrole polyamide skeleton
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An efficient and general route towards the synthesis of a series of chiral pyrrolidine pyrrole polyamide distamycin analogues starting from (L)-hydroxyproline is described. The binding abilities of these chiral pyrrolidine containing molecules to calf thymus DNA were evaluated by duplex DNA melting temperature analysis. The results revealed that both the chirality at the pyrrolidine ring and the site of incorporation plays an important role for binding at the duplex DNA.
- Lin, Chun-Yu,Yang, Ya-Ting,Ong, Chi Wi
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experimental part
p. 436 - 442
(2012/07/27)
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- Importance of ring puckering versus interstrand hydrogen bonds for the conformational stability of collagen
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Mismatch is fine: Proline derivatives with a ring pucker mismatching that of natural collagen but with favorable torsional angles along the peptide chain are readily tolerated within the collagen triple helix (see picture). In contrast, a competition between intramolecular and interstrand H bonds destabilizes the collagen triple helix. Copyright
- Erdmann, Roman S.,Wennemers, Helma
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supporting information; experimental part
p. 6835 - 6838
(2011/09/19)
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- MELANOCORTIN RECEPTOR AGONISTS
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The present invention relates to a compound having a good agonistic activity to melanocortin receptor, or pharmaceutically acceptable salt or isomer thereof, and an agonistic composition for melanocortin receptor comprising the same as an active ingredient.
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Page/Page column 10
(2010/06/11)
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- MELANOCORTIN RECEPTOR AGONISTS
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The present invention relates to a compound having a good agonistic activity to melanocortin receptor, or pharmaceutically acceptable salt or isomer thereof, and an agonistic composition for melanocortin receptor comprising the same as an active ingredient.
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Page/Page column 22
(2010/06/15)
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- Novel chemotactic For-Met-Leu-Phe-OMe (fMLF-OMe) analogues based on Met residue replacement by 4-amino-proline scaffold: Synthesis and bioactivity
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cis-(2S,4S) 4-Amino-proline (cAmp) and trans-(2S,4R) 4-amino-proline (tAmp) residues, bearing N-For or N-Boc substituents at the two amino groups, have been incorporated into the potent chemotactic agent fMLF-OMe in place of the N-terminal native (S)-methionine to give the analogues 17a-19a and 17b-19b. The new ligands have been examined for their activity (chemotaxis, superoxide anion production and lysozyme release) on human neutrophils as agonists and antagonists. Compounds 19a and 19b, bearing two N-For groups at the proline scaffold, are active and selective chemoattractants. The ligand 18b, containing N-For at the 4-amino group of the N-Boc-tAmp residue, exhibits significant chemotactic antagonism. The influence of the different substitution at the N-terminal position of the new analogues is discussed.
- Torino, Domenica,Mollica, Adriano,Pinnen, Francesco,Feliciani, Federica,Spisani, Susanna,Lucente, Gino
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experimental part
p. 251 - 259
(2011/03/19)
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- DUAL-ACTING ANTIHYPERTENSIVE AGENTS
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The invention relates to compounds having the formula: (I) wherein: Ar, r, R3, Z, X, and R5-7 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
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Page/Page column 84
(2009/04/25)
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- MELANOCORTIN RECEPTOR AGONISTS
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The present invention relates to a compound of the following formula 1, pharmaceutically acceptable salt and isomer thereof effective as agonist of melanocortin receptor, and an agonistic composition of melanocortin receptor comprising the same as active ingredient.
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Page/Page column 25
(2008/06/13)
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- Design, synthesis, and preliminary evaluation of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives as potential iNOS inhibitors
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A series of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives were synthesized and evaluated for their abilities to inhibit inducible nitric oxide synthase (iNOS) isoform. All target compounds were prepared in 11 steps from commercially trans-4-hydroxy-l-proline. The preliminary pharmacological test showed that three compounds, 17, 21, and 30, have the good potency (IC50 = 2.36, 2.68, 2.5 μM, respectively) which are compared to the NOS inhibitor NG-nitroarginine(L-NNA) (IC50 = 14.74 μM), and could be used as lead compounds for exploring new iNOS inhibitors in the future.
- Liu, Feng-Zhi,Fang, Hao,Zhu, Hua-Wei,Wang, Qiang,Yang, Yue,Xu, Wen-Fang
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p. 578 - 585
(2008/04/12)
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- Synthesis of enantiopure 1-azaspiro[4.5]dec-6-en-8-ones from l-proline derivatives
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An enantioselective synthesis of protected 1-azaspiro[4.5]dec-6-en-8-one derivatives was achieved using an alkylidene carbene 1,5-CH insertion reaction as the key step.
- Diaba, Faiza,Ricou, Eva,Bonjoch, Josep
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p. 1437 - 1443
(2007/10/03)
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- 1-((S)-γ-Substituted prolyl)-(S)-2-cyanopyrrolidine as a novel series of highly potent DPP-IV inhibitors
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1-(γ-Substituted prolyl)-(S)-2-cyanopyrrolidines were designed based on the predicted binding mode of the known DPP-IV inhibitor NVP-DPP728 and evaluated for their inhibitory activity. In structure-activity relationship study at the γ-position of proline,
- Sakashita, Hiroshi,Kitajima, Hiroshi,Nakamura, Mitsuharu,Akahoshi, Fumihiko,Hayashi, Yoshiharu
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p. 2441 - 2445
(2007/10/03)
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- PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
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The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
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- Synthesis and biological activity of 1-phenylsulfonyl-4-phenylsulfonylaminopyrrolidine derivatives as thromboxane A2 receptor antagonists
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The synthesis and biological activity of novel 1-phenylsulfonyl-4- phenylsulfonylaminopyrrolidine analogues are described. All compounds were produced through modification of the substituent formally corresponding to the 1,3-dioxane ring system and the ω-octenol side chain of thromboxane A2 (TXA2), in reference to the structure of Daltroban. Several compounds were found to be potent TXA2 receptor antagonists. Compound 51a was the most effective inhibitor of 9,11-epoxymethano PGH2 (U-46619)-induced rat aortic strip contraction (IC50 = 0.48 nM).
- Marusawa, Hiroshi,Setoi, Hiroyuki,Sawada, Akihiko,Kuroda, Akio,Seki, Jiro,Motoyama, Yukio,Tanaka, Hirokazu
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p. 1399 - 1415
(2007/10/03)
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- Synthesis of N(α)-(pyrinyl/pyrimidinyl acetyl)-4-aminoproline diastereomers with potential use in PNA synthesis
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This paper describes an approach to introduce conformational constraint and chirality into the PNA backbone by bridging the ethylenediamine and glycine components of thesame unit by a methylene group which leads to PNA based on 4-aminoprolyl backbone with chirality at C-4 and C-2. The synthesis and characterisation of all four diasteroisomers with thymine (T) as the sidechain nucleobase (3a-d) and the synthesis of one of the stereoisomer (2S, 4R) linked to each of the four nucleobases (10-13) are described. Using these monomeric units, two model dimers (17, 18) containing four chiral centres but differing in stereochemistry at only one site were prepared and CD data on these indicate considerable structural differences in base stacking induced by chiral backbone among these.
- Gangamani, Bargur P.,Kumar, Vaijayanti A.,Ganesh, Krishna N.
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p. 15017 - 15030
(2007/10/03)
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- N-SULFONYLINDOLINE DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS IN WHICH THEY ARE PRESENT
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The invention relates to N-sulfonyl derivatives of formulae (I) " and (I)' STR1 and to pharmaceutical compositions in which they are present. The compounds have an affinity for the vasopressin and ocytocin receptors. "
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