30992-29-1Relevant articles and documents
Conformational heterogeneity of a turn mimetic pseudo-peptide: Comparison of crystal state, solution and theoretically derived structures
Majia, Samir Kumar,Haldar, Debasish,Bhattacharyya, Dhananjay,Banerjee, Arindam
, p. 111 - 123 (2003)
Crystal structure analysis of the pseudo-peptide (tert-ButylN-{2-[N-(N,N′-dicyclohexyl- ureidocarbonylethyl)carbamoyl]prop-2-yl} carbamate) exhibited presence of a 13-membered intramolecular hydrogen bonded structure involving Boc C=O and Urea NH group to form an α-turn mimic [Acta Crystallogr. C 56 (2000) 1120]. However, NMR studies of this compound in CDCl3 using DMSO solvent titration of amide NH groups have revealed that the pseudo-peptide lacks of unique conformational state in solution. We have therefore carried out ab initio quantum mechanical calculations at up to B3LYP/6-31G** using density function theory level to characterise relative stabilities of different possible conformations with distinctive hydrogen bonding patterns. Computational studies also reveal that a 13-atom hydrogen bonded turn, identical to the crystal state conformation and analogous to the α-turn (in proteins) is energetically most stable. The structures with 7-atom hydrogen bonded turn (γ-turn) and with bifurcated hydrogen bonds are, however, seen to have energies quite comparable to that of the αturn mimetic. This indicates possibility of existence of multiple conformational states, corresponding to various turn structures (viz. α-turn mimetic, γ-turn, etc.) which may interconvert in NMR time scale.
Sensing of the Induced Helical Chirality by the Chiroptical Response of the Ferrocene Chromophore
?utalo, Petar,Kodrin, Ivan,Nuskol, Marko,Semen?i?, Mojca ?aki?
, (2021/12/27)
The experimental (infrared, nuclear magnetic resonance, circular dichroism) and computational (density functional theory) methods allowed us to demonstrate the potential of the ferrocene chromophore to translate chiral information stored at N-terminally attached l-Ala, and transmitted through achiral (Aib)n sequence (n=1 to 3), into a characteristic signal in circular dichroism spectra near 470 nm. The sufficiently long tetrapeptide forms a robust and highly organized 310 helices capable of perturbing the environment of the highly symmetric ferrocene chromophore in an asymmetric manner. The origin of the sign in the circular dichroism spectra of the ferrocene chromophore (near the 470 nm) strongly correlates with the sign of the dihedral angle χ, accounting for a rotation of a substituent attached to the cyclopentadienyl ring that depends on the helicity of peptide sequence. These observations may help us in the design of future ferrocene-based probes for the assignment of the screw-sense preference of short peptides.
Novel cilengitide-based cyclic RGD peptides as αvβ3 integrin inhibitors
Dangi, Abha,Marelli, Udaya Kiran,Meena, Chhuttan L.,Reichart, Florian,Sanjayan, Gangadhar J.,Singh, Dharmendra,Zahler, Stefan,Weinmüller, Michael
supporting information, (2020/02/28)
In this letter, we report a series of five new RGD-containing cyclic peptides as potent inhibitors to αvβ3 integrin protein. We have incorporated various unnatural lipophilic amino acids into the cyclic RGD framework of cilengitide, which is selective for αvβ3 integrin. All the newly synthesized cyclic peptides were evaluated in vitro solid phase binding assay and investigated for their binding behaviour towards integrin subtypes. All the cyclic peptides were synthesized in excellent yield following solution-phase coupling strategy. The cyclic RGD peptides 1a-e exhibited IC50 of 9.9, 5.5, 72, 11 and 3.3 nM, respectively, towards αvβ3 integrin protein. This finding offers further opportunities for the introduction unusual amino acids into the cyclic peptide framework of cilengitide.
Discovery of Selective Inhibitors of Endoplasmic Reticulum Aminopeptidase 1
Maben, Zachary,Arya, Richa,Rane, Digamber,An, W. Frank,Metkar, Shailesh,Hickey, Marc,Bender, Samantha,Ali, Akbar,Nguyen, Tina T.,Evnouchidou, Irini,Schilling, Roger,Stratikos, Efstratios,Golden, Jennifer,Stern, Lawrence J.
, p. 103 - 121 (2020/02/20)
ERAP1 is an endoplasmic reticulum-resident zinc aminopeptidase that plays an important role in the immune system by trimming peptides for loading onto major histocompatibility complex proteins. Here, we report discovery of the first inhibitors selective for ERAP1 over its paralogues ERAP2 and IRAP. Compound 1 (N-(N-(2-(1H-indol-3-yl)ethyl)carbamimidoyl)-2,5-difluorobenzenesulfonamide) and compound 2 (1-(1-(4-acetylpiperazine-1-carbonyl)cyclohexyl)-3-(p-tolyl)urea) are competitive inhibitors of ERAP1 aminopeptidase activity. Compound 3 (4-methoxy-3-(N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)sulfamoyl)benzoic acid) allosterically activates ERAP1's hydrolysis of fluorogenic and chromogenic amino acid substrates but competitively inhibits its activity toward a nonamer peptide representative of physiological substrates. Compounds 2 and 3 inhibit antigen presentation in a cellular assay. Compound 3 displays higher potency for an ERAP1 variant associated with increased risk of autoimmune disease. These inhibitors provide mechanistic insights into the determinants of specificity for ERAP1, ERAP2, and IRAP and offer a new therapeutic approach of specifically inhibiting ERAP1 activity in vivo.
Heteroannulation of Arynes with α-Amino Imides: Synthesis of 2,2-Disubstituted Indolin-3-ones and Application to the Enantioselective Total Synthesis of (+)-Hinckdentine A
Torres-Ochoa, Rubén O.,Buyck, Thomas,Wang, Qian,Zhu, Jieping
supporting information, p. 5679 - 5683 (2018/04/26)
A novel heteroannulation reaction between α-amino imides and in situ generated arynes has been developed for the synthesis of 2,2-disubstituted indolin-3-ones. An enantioselective total synthesis of the marine alkaloid (+)-hinckdentine A was subsequently accomplished using this reaction as a key step. A catalytic enantioselective Michael addition of an α-aryl-α-isocyanoacetate to phenyl vinyl selenone was employed for the construction of the enantioenriched α-quaternary α-amino ester.
C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS
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Page/Page column 28; 29, (2018/03/06)
The present invention relates to C-3 novel triterpenone with C-17 reverse amide compounds of Formula (I); and pharmaceutically acceptable salts thereof, wherein ring Formula (II), R1, R2, R3, R4, R5, R6, R7, 'n' and 'm' are as defined in Formula (I). The invention also relates to C-3 novel triterpenone with C-17 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Page/Page column 349, (2018/06/30)
Compounds of formula (I') and methods of their use and preparation, as well as compositions comprising compounds of formula (I').
INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Page/Page column 349, (2017/09/02)
The present disclosure is directed to compounds of formula I and methods of their use and preparation, as well as compositions comprising compounds of formula I.
NOVEL SUBSTITUTED AMIDES OF TRITERPENE DERIVATIVES AS HIV INHIBITORS
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Page/Page column 24, (2017/02/28)
The present invention relates to compounds of novel substituted amides of triteripene derivatives of formula (I); or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y, Z1, Z2, Z3 and formula (II) are as defined herein. The present invention also relates to,, and pharmaceutical compositions comprising compounds of formula (I) useful for the treatment of viral diseases and particularly HIV mediated diseases.
C-3 NOVEL TRITERPENONE WITH C-28 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS
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Page/Page column 39, (2016/11/21)
Formula (I) The invention relates to C-3 novel triterpenone with C-28 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
