- Hydrogen-Borrowing Alkylation of 1,2-Amino Alcohols in the Synthesis of Enantioenriched γ-Aminobutyric Acids
-
For the first time we have been able to employ enantiopure 1,2-amino alcohols derived from abundant amino acids in C?C bond-forming hydrogen-borrowing alkylation reactions. These reactions are facilitated by the use of the aryl ketone Ph*COMe. Racemisation of the amine stereocentre during alkylation can be prevented by the use of sub-stoichiometric base and protection of the nitrogen with a sterically hindered triphenylmethane (trityl) or benzyl group. The Ph* and trityl groups are readily cleaved in one pot to give γ-aminobutyric acid (GABA) products as their HCl salts without further purification. Both steps may be performed in sequence without isolation of the hydrogen-borrowing intermediate, removing the need for column chromatography.
- Hall, Christopher J. J.,Goundry, William R. F.,Donohoe, Timothy J.
-
supporting information
p. 6981 - 6985
(2021/03/01)
-
- INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
-
The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
- -
-
Paragraph 409; 410; 414
(2016/10/11)
-
- Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling
-
We report the development of a new class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in the remote desymmetrization of diarylmethanes via copper-catalyzed Ullman cross-coupling. Through design of these peptides, high levels of enantioinduction and good isolated yields were achieved in the long-range asymmetric cross-coupling (up to 93:7 er and 76% yield) between aryl bromides and malonates. Our mechanistic studies suggest that distal stereocontrol is achieved through a Cs-bridged interaction between the Lewis-basic C-terminal carboxylate of the peptides with the distal arene of the substrate.
- Kim, Byoungmoo,Chinn, Alex J.,Fandrick, Daniel R.,Senanayake, Chris H.,Singer, Robert A.,Miller, Scott J.
-
supporting information
p. 7939 - 7945
(2016/07/07)
-
- A COMPOUND FOR INHIBITING 11B-HYDROXY STEROID DEHYDROGENASE 1, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
Disclosed are a novel compound or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including the same for inhibiting human 11-β-hydroxy steroid dehydrogenase type 1 (11β-HSD1). The disclosed compound and the pharmaceutical composition including the same for inhibiting human 11-β-hydroxy steroid dehydrogenase type 1 (11β-HSD1) are excellent in activity and solubility, and is more efficient in formulation and transfer.
- -
-
Paragraph 0449-0451
(2014/08/06)
-
- A COMPOUND FOR INHIBITING 11BETA-HYDROXY STEROID DEHYDROGENASE 1, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
Disclosed are a novel compound or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including the same for inhibiting human 11-beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1). The disclosed compound and the pharmaceutical composition including the same for inhibiting human 11-beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1) are excellent in activity and solubility, and is more efficient in formulation and transfer.
- -
-
Paragraph 821-823
(2013/03/26)
-
- OxymaPure/DIC: An efficient reagent for the synthesis of a novel series of 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino] benzoyl amino acid ester derivatives
-
OxymaPure (ethyl 2-cyano-2-(hydroxyimino)acetate) was tested as an additive for use in the carbodiimide (DIC) approach for the synthesis of a novel series of α-ketoamide derivatives (4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino] benzoyl amino acid ester derivatives). OxymaPure showed clear superiority to HOBt/DIC or carbodiimide alone in terms of purity and yield. The title compounds were synthesized via the ring opening of N-acylisatin. First, N-acetylisatin was reacted with 4-aminobenzoic acid under conventional heating as well as microwave irradiation to afford 4-(2-(2-acetamidophenyl)-2-oxoacetamido)benzoic acid. This α-ketoamide was coupled to different amino acid esters using OxymaPure/DIC as a coupling reagent to afford 4-[2-(2-acetylaminophenyl)-2- oxoacetylamino] benzoyl amino acid ester derivatives in excellent yield and purity. The synthesized compounds were characterized using FT-IR, NMR, and elemental analysis.
- El-Faham, Ayman,Al Marhoon, Zainab,Abdel-Megeed, Ahmed,Albericio, Fernando
-
p. 14747 - 14759
(2014/01/17)
-
- CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
-
Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of formulae Ia and Ib are constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. These macrocycles Ia and Ib are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being the agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), ion channels and signal transduction pathways. In particular, these macrocycles act as antagonists of the motilin receptor, the FP receptor and the purinergic receptors P2Y1, as modulators of the serotonin receptor of subtype 5-HT2B, as blockers of the voltage-gated potassium channel Kv1.3 and as inhibitors of the β-catenin-dependent “canonical” Wnt pathway. Thus they are showing great potential as medicaments for a variety of diseases.
- -
-
Page/Page column 116
(2012/11/07)
-
- SUBSTITUTED IMIDAZOLONE DERIVATIVES, PREPARATIONS AND USES
-
The present invention relates to polysubstituted imidazolone derivatives, to the pharmaceutical compositions comprising them and to the therapeutic uses thereof in the human and animal health fields. The present invention also relates to a process for preparing these derivatives.
- -
-
Page/Page column 36
(2010/02/16)
-
- MONOCYCLIC CGRP RECEPTOR ANTAGONISTS
-
The present invention is directed to compounds of the formula (I) : (wherein variables A1, A2, A3, A4, A5, A6, A7, A8, G1, G2, G3, G4, J, Q, Ea, Eb, Ec, R6, R7, RPG and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
- -
-
Page/Page column 71
(2009/10/22)
-
- A PYRAZOLO[1,5-A]PYRIMIDINE COMPOUND
-
The present invention provides a pyrazolo[1,5-a]pyrimidine compound, having CB1 receptor-antagonizing activity, of the following formula [I]: in which R1 and R2 are the same or different and each an optionally substituted aryl group etc, R0 is hydrogen atom, an alkyl group etc, E is a group of the formula: -C(=O)- or -SO?2#191-, R is a group of the following formula [i], [ii] or [iii] etc: Ring A is (a) a C?3-8#191 cycloalkyl group optionally fused to a benzene ring or (b) a benzene ring, Q is a single bond or a methylene group, Ring B is a 4- to 7-membered aliphatic heterocyclic group, said cyclic group binding via its ring-carbon atom to the adjacent nitrogen atom, X is sulfur atom etc, R3 is an alkyl group optionally substituted by an alkylthio group, R4 is hydrogen atom, an alkyl group etc, one of RA and RB is an alkyl group etc, and the other is hydrogen atom, an alkyl group etc, or a pharmaceutically acceptable salt thereof.
- -
-
Page/Page column 82
(2008/06/13)
-
- PYRAZOLE DERIVATIVES AS THERAPEUTIC AGENTS
-
Salts of 1,5-diarylpyrazole-3-carboxamides and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.
- -
-
Page/Page column 46
(2010/11/26)
-
- Substituted monocyclic CGRP receptor antagonists
-
Compounds of formula I: (wherein variables A1, A2, A3, A4, m, n, J, Q, R4, Ea, Eb, Ec, R6, R7, Re, Rf, RPG and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
- -
-
Page/Page column 49
(2008/06/13)
-
- PREPARATION AND USE OF BIPHENYL-4-YL-CARBONYLAMINO ACID DERIVATIVES FOR THE TREATMENT OF OBESITY
-
This invention relates to certain biphenyl-4-yl carbonylamino acid compounds, compositions, and methods for treating or preventing obesity and related diseases.
- -
-
Page/Page column 35-36
(2010/11/08)
-
- Ultrasound accelerated synthesis of proteinogenic and α,α- dialkylamino acid ester salts
-
A simple and efficient sonochemical esterification of proteinogenic as well as cyclic α,α-dialkyl amino acid methyl and ethyl ester hydrochloride salts employing thionyl chloride and alcohol has been reported. All the amino acid esters made have been obtained in good yield (94-98%) as pure compounds.
- Kantharaju,Babu, Vommina V. Suresh
-
p. 1942 - 1944
(2007/10/03)
-
- Privileged structure based ligands for melanocortin-4 receptors-Aliphatic piperazine derivatives
-
Aliphatic carbocyclic replacement of the benzyl group of compound 1 yielded compounds with high affinity for the melanocortin-4 receptor (MC4R). Compounds with a cyclohexyl group showed a consistent high affinity, while different polar groups with less basicity were good replacements for the original diethyl amines. Substitution of the polar group found in these privileged structures with an aliphatic moiety produced compounds with high affinity for MC4R.
- Briner, Karin,Collado, Iván,Fisher, Matthew J.,García-Paredes, Cristina,Husain, Saba,Kuklish, Steven L.,Mateo, Ana I.,O'Brien, Thomas P.,Ornstein, Paul L.,Zgombick, John,de Frutos, óscar
-
p. 3449 - 3453
(2007/10/03)
-
- CHEMICAL COMPOUNDS
-
Phosphoramidate derivatives of nucleotides and their use in the treatment of cancer are described. The base moieties of, for example, each of deoxyuridine, cytarabine, gemcitabine and citidine may be substituted at the 5-position. The phosphoramidate moiety has attached to the P atom an aryl-O moiety and an α-amino acid moiety. The α-amino acid moiety may correspond to or be derived from either a naturally occurring or a non-naturally occurring amino acid.
- -
-
Page/Page column 18; 20
(2010/02/10)
-
- THERAPEUTIC AGENTS
-
The present invention relates to compounds of formula (I) and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.
- -
-
Page/Page column 48
(2008/06/13)
-
- Biaryloxymethylarenecarboxylic acids as glycogen synthase activator
-
The present invention relates to compounds of formula (I) wherein R1, R2, R3, R4, m, n, p and s are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases that are associated with the activation of the glycogen synthase enzyme, such as diabetes.
- -
-
Page/Page column 39
(2010/02/10)
-
- GROWTH HORMONE SECRETAGOGUES
-
This invention relates to novel compounds which are useful in the modulation of endogenous growth hormone levels in a mammal. The invention further relates to novel intermediates for use in the synthesis of said compounds, as well as novel processes employed in these syntheses. Also included are methods of treating a mammal which include the administration of said compounds.
- -
-
Page/Page column 103-104
(2010/02/07)
-
- Certain thiol inhibitors of endothelin-converting enzyme
-
Disclosed as endothelin converting enzyme inhibitors are the compounds of the formula wherein the variables have the meanings as defined hereinbefore.
- -
-
-
- Substituted 2-arylimino heterocycles and compositions containing them, for use as progesterone receptor binding agents
-
This invention relates to 2-arylimino heterocycles, including 2-arylimino-1,3-thiazolidines, 2-arylimino-2,3,4,5-tetrahydro-1,3-thiazines, 2-arylimino-1,3-thiazolidin-4-ones, 2-arylimino-1,3-thiazolidin-5-ones, and 2-arylimino-1,3-oxazolidines, and their use in modulating progesterone receptor mediated processes, and pharmaceutical compositions for use in such therapies.
- -
-
Page column 31
(2010/02/05)
-
- Hydrogen-bonded tapes based on symmetrically substituted diketopiperazines: A robust structural motif for the engineering of molecular solids
-
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.
-
p. 11807 - 11816
(2007/10/03)
-
- Design and synthesis of 1-aminocycloalkane-1-carboxylic acid-substituted deltorphin analogues: unique delta and mu opioid activity in modified peptides.
-
Deltorphin analogues were substituted by a series of achiral C alpha,alpha-dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carboxylic acids, Ac chi c, where chi = a hexane, pentane, or propane cycloalkane ring) in position 2, 3, 4, or 2 and 3 in de
- Breveglieri, Angela,Guerrini, Remo,Salvadori, Severo,Bianchi, Clementina,Bryant, Sharon D.,et al.
-
p. 773 - 780
(2007/10/03)
-
- HETEROCYCLES FROM NITRILE IMINES. PART IV. CHIRAL 4,5-DIHYDRO-1,2,4-TRIAZIN-6-ONES
-
The reaction of nitrile imines (II) with α-amino esters (III) proceeds with no detectable racemization and constitutes a convenient synthetic route to 4,5-dihydro-1,2,4-triazin-6-ones (IV).Permangamate oxidation of heterocycles (IV) affords the corresponding 1,2,4-triazin-6-ones (V).The reaction of (II) with β-amino esters gives the respective acyclic amidrazone adducts (VI).
- El-Abadelah, Mustafa M.,Hussein, Ahmad Q.,Thaher, Bassam A.
-
p. 1879 - 1895
(2007/10/02)
-
- Peptide Sweeteners. 6. Structural Studies on the C-Terminal Amino Acid of L-Aspartyl Dipeptide Sweeteners
-
Stereochemical and structural aspects of the variations in the C-terminal residue of L-aspartyl-L-phenylalanine methyl ester have been investigated.Novel configurational analogues such as L-aspartyl-D-alanine benzyl ester and L-aspartyl-D-α-aminobutyric acid benzyl ester were found to be sweet.In addition, chiral and achiral α,α-dialkylglycine and α-aminocycloalkanecarboxylic acids were incorporated into the dipeptides.The L-aspartic acid based dipeptide derivatives of α-aminoisobutyric acid methyl ester, α-aminocyclopropanecarboxylic acid methyl ester, α-aminocyclobutanecarboxylic acid methyl ester, and α-aminocyclopentanecarboxylic acid methyl ester are sweet.Dipeptides with α-aminocyclohexanecarboxylic acid methyl ester and α-aminocycloheptanecarboxylic acid methyl ester are bitter, whereas the analogues with α-aminocyclooctanecarboxylic acid methyl ester, α,α-diethylglycine methyl ester, and α-aminoisobutyric acid benzyl ester are tasteless.Aspects on chirality and effective volume of the C-terminal residue are discussed and correlated with taste.
- Tsang, Joseph W.,Schmied, Bernhard,Nyfeler, Rolf,Goodman, Murray
-
p. 1663 - 1668
(2007/10/02)
-
- N-chloro-amino acid derivatives activity
-
There is provided, a novel class of compounds exhibiting antibacterial activity, said compounds having the formula: EQU1 wherein X and Y each represent a member which may be the same or different selected from the group consisting of H and Cl with the pri
- -
-
-