- Efficient synthesis of 2-aminoindane-2-carboxylic acid via dialkylation of nucleophilic glycine equivalent
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An efficient, easy to scale-up method for preparing 2-aminoindane-2-carboxylic acid via two-step alkylation of a Ni(II)-complex of glycine Schiff base with 2-[N-(αpicolyl)amino]benzophenone (PAAP) (2b) with o-dibromoxylylene (3) is reported. The first step, monoalkylation of 2b with 3, conducted under phase-transfer conditions, gave the corresponding complex 6 in excellent chemical yield (97.2%). Without any purification the intermediate 6 was cyclized under homogeneous conditions (DMF, NaO-t-Bu) to give the product 7 in high chemical yield (93.1%). Decomposition of prepared 7 afforded the target amino acid 2-aminoindane-2-carboxylic acid (1) in 97.9% yield, along with recovery of ligand 8, which was converted back to the starting glycine complex 2b. Operationally convenient experimental procedures, mild reaction conditions, as well as high chemical and volume yields render the method practical for preparing amino acid 1 and its analogues.
- Ellis, Trevor K.,Hochla, Veronica M.,Soloshonok, Vadim A.
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- PEPTIDYL NITRILCOMPOUNDS AS PEPTIDASE INHIBITORS
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The invention relates to compounds of Formula (II) and their use in theraphy as peptidase inhibitors.
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Page/Page column 110
(2012/09/22)
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- PEPTIDES AND PEPTIDOMIMETIC COMPOUNDS, THE MANUFACTURING THEREOF AS WELL AS THEIR USE FOR PREPARING A THERAPEUTICALLY AND/OR PREVENTIVELY ACTIVE PHARMACEUTICAL COMPOSITION
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Peptides, peptidomimetics and derivatives thereof of the general formula I: H2N-GHRPX1-β-X4X5X6X7X8X9X10-X11 (I), in which X1-X10 denote one of the 20 genetically coded amino acids, wherein X8, X9 and X10 may also denote a single chemical bond;X11 denotes OR1 in which R1 equals hydrogen or (C1-C10) alkyl NR2R3 with R2 and R3 are equal or different and denote hydrogen, (C1-C10) alkyl, or a residue —W-PEG5-60K, in which the PEG residue is attached via a suitable spacer W to the N-atom, ora residue NH—Y-Z-PEG5-60K, in whichY denotes a chemical bond or a genetically coded amino acids from the group S, C, K or R andZ denotes a spacer, via which a polyethylene glycol (PEG)-residue can be attached, and their physiologically acceptable salts, andβ denotes an amino acid, or a peptidomimetic element, which induces a bend or turn in the peptide backbone.
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- TOPOISOMERASE INHIBITORS
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The present invention provides compounds that are effective against inhibiting topoisomerase (i.e., topoisomerase I and/or topoisomerase II). These compounds are used for treating cell-proliferative disorders. In some instances, these compounds have antic
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Page/Page column 78-79
(2010/10/20)
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- Asymmetric synthesis of unusual α-amino acids
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The synthesis of enantiomerically pure non-proteinogenic bis and cyclic amino acids 3a,b and achiral amino acid 3c using chiral NiII complex 1 and α,α′-dibromo-o-xylene as a bifunctional agent of alkylation is presented.
- Belokon, Yuri N.,Kochetkov, Konstantin A.,Borkin, Dmitry A.
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p. 132 - 134
(2007/10/03)
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- Hydrogen-bonded tapes based on symmetrically substituted diketopiperazines: A robust structural motif for the engineering of molecular solids
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A series of eight symmetrically substituted diketopiperazines (DKPs) derived from 1-amino-1-carboxycycloalkanes (n = 3-7; 3,3,5,5-tetramethylcyclohexane; 4,4-dimethylcyclohexane; 2-indan) were synthesized and their crystal structures determined. In the solid state, all eight compounds form two pairs of hydrogen bonds with two adjacent molecules to form a one-dimensional structure that we refer to as 'tapes'. These molecules represent a range of volumes and shapes that contain a common molecular fragment (DKP ring). We examined this series of compounds with three objectives in mind: (i) to establish the ability of the hydrogen-bonded 'tape' motif to persist through these differences in volume and shape; (ii) to provide a series of structurally related compounds to use to test computational methods of predicting crystal structure from molecular structure; (iii) to search for qualitative correlations between molecular structure and crystal packing. All compounds form tapes and with one exception, all tapes pack with their long axes parallel. When viewed down their long axis, two types of tapes emerge: planar and nonplanar. The type of tape that forms reflects the conformation adapted by the DKP ring-planar or boat. Planar tapes form when the angle (α) between the two planes defined by the cis-amides in the DKP ring is 180°; nonplanar tapes form when α 180°. Five of the eight compounds studied form planar tapes, the remaining three compounds form nonplanar tapes. Despite the variability in volume and shape represented by this series of molecules, the persistence of the tape motif in their crystalline solids suggests that the hydrogen-bonding interactions between parallel alignment of tapes that pack in a manner that permits the interdigitation of substituents on adjacent tapes.
- Palacin, Serge,Chin, Donovan N.,Simanek, Eric E.,MacDonald, John C.,Whitesides, George M.,McBride, Mary T.,Palmore, G. Tayhas R.
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p. 11807 - 11816
(2007/10/03)
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- Hexapeptide anaphylatoxin-receptor ligands
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Oligopeptide compounds or oligopeptide analogue compounds of the formula A-B-D-E-G-J-L-M-Q are ligands for the anaphylatoxin receptor and are useful in the treatment of inflammatory disease states.Also disclosed are anaphylatoxin receptor ligand compositi
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- Inhibitors of Phenylalanin Ammonia-Lyase: 2-Aminoindan-2-phosphonic Acid and Related Compounds
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2-Aminoindan-2-phosphonic acid (3) was synthesized for the first time both directly from 2-indanone (7) as well as by alkylation of ethyl diethoxyphosphorylacetate with 1,2-bis(bromomethyl)benzene (9) via 10-12, respectively. 2-Hydroxyindan-2-phosphonic acid (5) was obtained also from 7 via its diisopropyl ester 8.Compound 3 was found to be a potent inhibitor of the plant enzyme phenylalanine ammonia-lyase (EC 4.3.1.5) both in vitro and in vivo.Of the related 2-aminoindan-2-carboxylic acid (4), compound 5, and 1-aminocyclopentylphosphonic acid (6), only 4 inhibited the enzyme but was far less inhibitory than 3. Key Words: 2-Aminoindan-2-phosphonic acid/Enzyme inhibition/Phenylalanine ammonia-lyase
- Zon, Jerzy,Amrhein, Nikolaus
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p. 625 - 628
(2007/10/02)
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- Conformational restriction of the phenylalanine residue in a cyclic opioid peptide analogue: Effects on receptor selectivity and stereospecificity
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In an effort to determine the effect of side chain conformational restriction on opioid receptor selectivity, the cyclic phenylalanine analogues 2-aminoindan-2-carboxylic acid (Aic), 2-aminotetralin-2-carboxylic acid (Atc), and tetrahydroisoquinoline-3-carboxylic acid (Tic) were substituted for Phe in the potent cyclic opioid peptide analogue H-Tyr-D-Orn-Phe-Glu-NH2, which lacks significant opioid receptor selectivity. Compounds were tested in μ- and δ-opioid receptor representative binding assays and bioassays in vitro. The analogue H-Tyr-D-Orn-Aic-Glu-NH2 was found to be a potent agonist with high preference of μ receptors over δ receptors. Opening of the five-membered ring of Aic in the latter peptide, as achieved through substitution of C(α)-methylphenylalanine or o-methylphenylalanine, resulted in only slightly selective compounds, indicating that the high μ selectivity of the Aic analogue is exclusively the consequence of the imposed side chain conformational restriction. Both diastereoisomers of H-Tyr-D-Orn-(D,L)-Atc-Glu-NH2 were highly μ-selective and, in contrast to the weak affinity observed with the D-Phe3 analogue as compared to the L-Phe3 analogue, both had similar potency. Thus, stereospecificity was lost as a consequence of side chain conformational restriction. Further structure-activity data obtained with analogues containing L- or D-homophenylalanine (Hfe) or 3-(1'-naphthyl)alanine (Nap) in place of Phe3 and consideration of geometric interrelationships between Nap and the L and D isomers of Atc, Hfe, and Phe led to the proposal that the D-Phe3 and the D-Atc3 analogue may have different modes of binding to the receptor. The very low potency observed with H-Tyr-D-Orn-N(α)MePhe-Glu-NH2 (N(α)MePhe = N(α)-methylphenylalanine) and H-Tyr-D-Orn-Tic-Glu-NH2 indicated that N(α)-alkylation at the 3-position is detrimental to activity.
- Schiller,Weltrowska,Nguyen,Lemieux,Chung,Marsden,Wilkes
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p. 3125 - 3132
(2007/10/02)
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