- Development of a dual fluorogenic and chromogenic dipeptidyl peptidase IV substrate
-
A new far-red dual fluorogenic and chromogenic substrate, 5-glycylprolylglycylprolyl-9-di-3-sulfonyl-propylaminobenza[a]phenoxazonium perchlorate (GPGP-2SBPO), was developed for dipeptidyl peptidase IV (DPP-IV) sensing. The glycylprolylglycylprolyl tetrapeptide was chosen as the recognition sequence due to its stability under physiological conditions. In contrast, the truncated substrate, GP-2SBPO, containing only a glycylprolyl peptide, is unstable. Proteolysis of GPGP-2SBPO was assayed by monitoring the absorbance and fluorescence signals from the released fluorochrome, 2SBPO, at 625 and 670 nm, respectively.
- Ho, Nan-Hui,Weissleder, Ralph,Tung, Ching-Hsuan
-
-
Read Online
- Molecular capture and conformational change of diketopiperazines containing proline residues by epigallocatechin-3-O-gallate in water
-
The addition of an aqueous solution of diketopiperazine cyclo(Pro-Xxx) (Xxx: amino acid residue) to an aqueous solution of (?)-epigallocatechin-3-O-gallate (EGCg) led to precipitation of the complex of EGCg and cyclo(Pro-Xxx). The molecular capture abilities of cyclo(Pro-Xxx) using EGCg were evaluated by the ratio of the amount of cyclo(Pro-Xxx) included in the precipitates of the complex with EGCg to that of the total cyclo(Pro-Xxx) used. Stronger hydrophobicity of the side chain of the amino acid residue of cyclo(Pro-Xxx) led to a higher molecular capture ability. Furthermore, the molecular capture ability decreased when the side chain of the amino acid residue had a hydrophilic hydroxyl group. When diketopiperazine cyclo(Pro-Xxx), excluding cyclo(D-Pro-L-Ala), was taken into the hydrophobic space formed by the three aromatic A, B, and B′ rings of EGCg, and formed a complex, their conformation was maintained in the hydrophobic space. Based on nuclear Overhauser effect (NOE) measurement, the 3-position methyl group of cyclo(D-Pro-L-Ala) in D2O was axial, whereas that of cyclo(L-Pro-L-Ala) was equatorial. When cyclo(D-Pro-L-Ala) was taken into the hydrophobic space of EGCg and formed a 2:2 complex, its 3-position methyl group changed from the axial position to the equatorial position due to steric hindrance by EGCg.
- Ishizu, Takashi,Tokunaga, Miku,Fukuda, Moeka,Matsumoto, Mana,Goromaru, Takeshi,Takemoto, Soushi
-
p. 585 - 589
(2021/06/06)
-
- En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal-Organic Framework Catalysts
-
Peptide bond formation is a challenging, environmentally and economically demanding transformation. Catalysis is key to circumvent current bottlenecks. To date, many homogeneous catalysts able to provide synthetically useful methods have been developed, while heterogeneous catalysts remain largely restricted to the studies addressing the prebiotic formation of peptides. Here, the catalytic activity of Zr6-based metal-organic frameworks (Zr-MOFs) toward peptide bond formation is investigated using dipeptide cyclization as a model reaction. Unlike previous catalysts, Zr-MOFs largely tolerate water, and reactions are carried out under ambient conditions. Notably, the catalyst is recyclable and no additives to activate the COOH group are necessary, which are common limitations of previous methods. In addition, a broad reaction scope tolerates substrates with bulky and Lewis basic groups. The reaction mechanism was assessed by detailed mechanistic and computational studies and features a Lewis acid activation of carboxylate groups by Zr centers toward amine addition in which an alkoxy ligand on adjacent Zr sites assists in lowering the barrier of key proton transfers. The proposed concepts were also used to study the formation of intermolecular peptide bond formation. While intrinsic challenges associated with the catalyst structure and water removal limit a more general intermolecular reaction scope under current conditions, the results suggest that further design of Zr-MOF catalysts could render these materials broadly useful as heterogeneous catalysts for this challenging transformation.
- Conic, Dragan,De Azambuja, Francisco,Harvey, Jeremy N.,Loosen, Alexandra,Parac-Vogt, Tatjana N.,Van Den Besselaar, Maxime
-
p. 7647 - 7658
(2021/06/30)
-
- Highly Diastereoselective Synthesis of Cyclic α-Aminophosphonic and α-Aminophosphinic Acids from Glycyl-l-Proline 2,5-Diketopiperazine
-
This paper describes the first diastereoselective synthesis of cyclic α-aminophosphonic and α-amino phosphonic acids from glycyl-l-proline 2,5-diketopiperazine (S)-6 prepared according to the usual peptide coupling procedures. The highlights of this contribution is the chemoselective reduction of the carbamate-imide activated carbonyl group in the N-Boc 2,5-diketopiperazine (S)-11 to generate the unstable hemiaminals (1R,8aS)-12 and (1S,8aS)-13, followed by the highly diastereoselective nucleophilic addition of trimethyl phosphite or dimethyl phenylphosphonite to the chiral carbenium ion (S)-5. Acid hydrolysis of the phosphonate and phosphinate functionalities with simultaneous cleavage of the tert-butyl carbamate protecting group led to the target compounds. The high diastereoselectivity in the nucleophilic addition of trivalent phosphorus to the chiral carbenium ion (S)-5 is in agreement with our precedent reports.
- Ordó?ez, Mario,Torres-Hernández, Fernando,Viveros-Ceballos, José Luis
-
p. 7378 - 7383
(2019/11/26)
-
- Total Synthesis of Tryprostatin B: Synthesis and Asymmetric Phase-Transfer-Catalyzed Reaction of Prenylated Gramine Salt
-
A concise and efficient total synthesis of microtubule inhibitor tryprostatin B (1) is described. The key step is the preparation of a diprenylated gramine salt 9a. In this step, the prenyl group is incorporated at the 2-position of the indole moiety by direct lithiation of the Boc-protected gramine. We also developed and optimized the asymmetric phase-transfer-catalyzed reaction with salt 9a to provide the C2-prenyl tryptophan intermediate 2 resulting in 93% enantiomeric excess (ee) and 65% yield. The total synthesis of 1 is done in six steps with 35% overall yield.
- Huisman, Matthew,Rahaman, Mizzanoor,Asad, Sharif,Oehm, Sarah,Novin, Sherwin,Rheingold, Arnold L.,Hossain, M. Mahmun
-
p. 134 - 137
(2019/01/04)
-
- Water-Tolerant and Atom Economical Amide Bond Formation by Metal-Substituted Polyoxometalate Catalysts
-
A simple, safe, and inexpensive amide bond formation directly from nonactivated carboxylic acids and free amines is presented in this work. Readily available Zr(IV)- and Hf(IV)-substituted polyoxometalates (POM) are shown to be catalysts for the amide bond formation reaction under mild conditions, low catalyst loading, and without the use of water scavengers, dry solvents, additives for facilitating the amine attack, or specialized experimental setups commonly employed to remove water. Detailed mechanistic investigations revealed the key role of POM scaffolds which act as inorganic ligands to protect Zr(IV) and Hf(IV) Lewis acidic metals against hydrolysis and preserve their catalytic activity in amide bond formation reactions. The catalysts are compatible with a range of functional groups and heterocycles useful for medicinal, agrochemical, and material chemists. The robustness of the Lewis acid-POM complexes is further supported by the catalyst reuse without loss of activity. This prolific combination of Zr(IV)/Hf(IV) and POMs inaugurates a powerful class of catalysts for the amide bond formation, which overcomes key limitations of previously established Zr(IV)/Hf(IV) salts and boron-based catalysts.
- De Azambuja, Francisco,Parac-Vogt, Tatjana N.
-
p. 10245 - 10252
(2019/11/03)
-
- CERTAIN PROTEIN KINASE INHIBITORS
-
Provided are certain CDK4/6 inhibitors, pharmaceutical compositions thereof, and methods of use therefor.
- -
-
-
- The compound for anti-skin aging and skin wrinkle improving
-
Provided is a composition applicable to alleviate skin wrinkles by obtaining and using particular components derived from salted seafood through extraction. Preferably, the compound can be used as a cosmetic composition comprising at least one among composition 1: L-Pro-L-Tyr, composition 2: L-Pro-L-Phe, and composition 3: L-Pro-L-Val. By using natural materials derived from salted seafood, a novel material free of side effects can be easily obtained, and an effect of reducing costs of production can be obtained accordingly. Also, materials which can be applied on the exterior of the skin can be obtained. Thus, suggested is a novel way to alleviate skin wrinkles by using naturally derived materials.COPYRIGHT KIPO 2016
- -
-
Paragraph 0064; 0065
(2017/06/10)
-
- A general method for the facile synthesis of optically active 2-substituted piperazines via functionalized 2,5-diketopiperazines
-
Upon utilization of some common methods described in the literature for the synthesis of chiral, 2-substituted 2,5-diketopiperazines, extensive racemization was observed. Further investigation showed that heating in the presence of a mild base racemized the chiral center in the product diketopiperazines. A generalized, readily scalable route was sought and, after investigating the effect of base and temperature, conditions were identified that promoted cyclization without erosion of enantiomeric excess. An array of functionalization was tolerated and this procedure serves as a useful and reliable method for the facile synthesis of this important class of compounds.
- Ashton, Kate S.,Denti, Mitchell,Norman, Mark H.,St. Jean Jr., David J.
-
p. 4501 - 4504
(2014/08/05)
-
- AGRICULTURAL CHEMICAL CONTAINING 2,5-DIKETOPIPERAZINE DERIVATIVE AS ACTIVE INGREDIENT
-
Disclosed herein is an agricultural agent containing a 2,5-diketopiperazine derivative capable of controlling plant diseases and promoting plant growth or an agriculturally acceptable salt thereof as an active ingredient.
- -
-
Paragraph 0033
(2013/06/05)
-
- Development of a diketopiperazine-forming dipeptidyl Gly-Pro spacer for preparation of an antibody-drug conjugate
-
We developed a novel diketopiperazine-forming dipeptidyl spacer aimed at application in antibody-drug conjugates. Enzymatic cleavage of a peptide linked to the Gly-Pro spacer resulted in formation of diketopiperazine, which was stable and non-toxic, and release of the parent drug. The Royal Society of Chemistry 2013.
- Manabe, Shino,Machida, Hikaru,Aihara, Yoshiyuki,Yasunaga, Masahiro,Ito, Yukishige,Matsumura, Yasuhiro
-
p. 792 - 796
(2013/08/26)
-
- A new benzotriazole-mediated stereoflexible gateway to hetero-2,5- diketopiperazines
-
Open chain Cbz-L-aa1-L-Pro-Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans- or cis-fused 2,5- diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans-DKPs (69-75%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (65-72%). A representative set of proline-containing cis- and trans-DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results. Stereoflexible route to DKPs: A convenient, versatile, and flexible benzotriazole-mediated methodology for the synthesis of proline-containing hetero-2,5-diketopiperazines (DKPs) is reported. Depending on the reaction conditions, either cis- or trans-configured DKPs were obtained starting from the same inexpensive l,l-dipeptidoyl benzotriazole key intermediate (see scheme). Kinetics, chiral HPLC, and computational studies forged a background for mechanistic rationalization. Copyright
- Monbaliu, Jean-Christophe M.,Hansen, Finn K.,Beagle, Lucas K.,Panzner, Matthew J.,Steel, Peter J.,Todadze, Ekaterina,Stevens, Christian V.,Katritzky, Alan R.
-
experimental part
p. 2632 - 2638
(2012/04/17)
-
- Direct acyl substitution of carboxylic acids: A chemoselective o- to N-acyl migration in the traceless staudinger ligation
-
A chlorophosphite-modified, Staudinger-like acylation of azides involving a highly chemoselective, direct nucleophilic acyl substitution of carboxylic acids is described. The reaction provides the corresponding amides with analytical purity in 32-97 % yield after a simple aqueous workup without the need for a pre-activation step. The use of chlorophosphites as dual carboxylic acid-azide activating agents enables the formation of acyl C-N bonds in the presence of a wide range of nucleophilic and electrophilic functional groups, including amines, alcohols, amides, aldehydes, and ketones. The coupling of carboxylic acids and azides for the formation of alkyl amides, sulfonyl amides, lactams, and dipeptides is described. Copyright
- Kosal, Andrew D.,Wilson, Erin E.,Ashfeld, Brandon L.
-
supporting information
p. 14444 - 14453,10
(2020/09/16)
-
- Cyclic dipeptides: Catalyst/promoter-free, rapid and environmentally benign cyclization of free amino acids
-
"The best catalyst is no catalyst." With growing public concern over global warming and the amount of greenhouse gases, it is important to reduce the amount of chemicals and eliminate waste, to obtain better results in a simple, selective, safe, and environmentally benign fashion compared to conventional tedious chemical synthesis. Herein, we disclose an environmentally benign, rapid, catalyst/promoter/coupling reagent-free cyclization procedure of free amino acids to furnish exclusively cyclic dipeptides (2,5- diketopiperazines, DKPs) in excellent or even quantitative yield, along with their solid state self-assembling properties. This process is extremely simple and highly efficient with little or no traditional synthetic skills and without any chromatographic purification. Synthesis of structurally diverse DKPs has been achieved with a dramatic decrease in the reaction time, the amount/number of solvents used, a significant increase in the yield and nearly complete elimination of waste. As a result, this is an excellent example for the environmentally benign, clean and green chemistry concept. The most exciting outcome of our investigation is an unusual case of chiral self-recognition encountered upon the cyclization of rac-pipecolic acid, which resulted in the formation of the meso-product exclusively.
- Nonappa,Ahonen, Kari,Lahtinen, Manu,Kolehmainen, Erkki
-
supporting information; experimental part
p. 1203 - 1209
(2011/06/26)
-
- Design, synthesis, and structure-activity relationship study of bicyclic piperazine analogs of indole-3-carboxamides as novel cannabinoid CB1 receptor agonists
-
Bicyclic piperazine derivatives were synthesized as conformationally constrained analogs of N-alkyl piperazines and were found to be potent CB1 receptor agonists. The CB1 receptor agonist activity was dependent upon the absolute configuration of the chiral center of the bicyclic ring system. Although the conformational constraint did not protect the compounds from metabolism by N-dealkylation, several bicyclic analogs were found to be more potent than the unconstrained lead compound. Compound 8b demonstrated potent antinociceptive activity in vivo.
- Moir, Elizabeth M.,Yoshiizumi, Kazuya,Cairns, Jim,Cowley, Phillip,Ferguson, Morag,Jeremiah, Fiona,Kiyoi, Takao,Morphy, Richard,Tierney, Jason,Wishart, Grant,York, Mark,Baker, James,Cottney, Jean E.,Houghton, Andrea K.,McPhail, Petula,Osprey, Andrew,Walker, Glenn,Adam, Julia M.
-
scheme or table
p. 7327 - 7330
(2011/01/12)
-
- An efficient green synthesis of proline-based cyclic dipeptides under water-mediated catalyst-free conditions
-
l-Proline-based cyclic dipeptides were synthesized from N-Boc-protected dipeptide methyl esters under catalyst-free condition using water as a solvent. One-pot deprotection and cyclization have been used as the key steps, providing an efficient and environmentally friendly approach. Clean reaction conditions, easy isolation, and good yields of cyclic dipeptides are the salient features of the proposed methodology.
- Thajudeen, Habeebullah,Park, Kyungseok,Moon, Surk-Sik,Hong, In Seok
-
scheme or table
p. 1303 - 1305
(2010/04/29)
-
- Diastereoselective alkylation of a proline-derived bicyclic lactim ether
-
N-Boc-protected L-proline (6) was converted into the bicyclic lactim ether (8aS)-6,7,8,8a-tetrahydro-1-methoxypyrrolo[1,2-a]pyrazin-4(3H)-one (5) in four steps (Scheme 1). Deprotonation with LDA or LHMDS and subsequent alkylation resulted in the diastereoisomeric products cis- and trans-9. The diastereoselectivity was mainly dependent on the electrophile. Whereas small alkyl halides gave preferably cis-9, sterically more-demanding alkyl halides resulted in cisltrans mixtures. Electrophiles bearing a π-system favored the trans-products 9. Some isolated cis- and tranx-lactim ethers 9 were converted to the corresponding diketopiperazines cis- and trans-10 by acid hydrolysis. The structures and configurations of several compounds were confirmed by NMR and NOE experiments, as well as by X-ray crystallography (Figs. 1-4).
- Hendea, Daniela,Laschat, Sabine,Baro, Angelika,Frey, Wolfgang
-
p. 1894 - 1909
(2007/10/03)
-
- PYRIMIDINE DERIVATIVE
-
This invention provides pyrimidine derivatives represented by a formula, in the formula, ring A stands for carbocyclic group or heterocyclic group, X 1 stands for hydrogen, lower alkyl, amino, etc., X 2 stands for hydrogen or lower alkyl, Y stands for a direct bond or sulfur or nitrogen, n stands for an integer of 0 - 4, and Ar stands for a group of the following formula, or a salt thereof, which concurrently exhibit 5-HT 1A agonistic activity and 5-HT 3 antagonistic activity and are useful for therapy and treatments of diseases such as IBS. The invention furthermore provides a therapeutic method of IBS, characterized by having 5-HT 1A agonistic activity and 5-HT 3 antagonistic activity work simultaneously and cooperatively in vivo, which comprises either administering 5-HT 3 antagonistic agent which concurrently exhibits 5-HT 1A agonistic activity, or administering 5-HT 1A agonistic agent and 5-HT 3 antagonistic agent simultaneously, in sequence or at an interval.
- -
-
Page/Page column 129
(2010/11/24)
-
- Cyclization-activated prodrugs. Synthesis, reactivity and toxicity of dipeptide esters of paracetamol
-
Dipeptide esters of paracetamol were prepared in high yields. These compounds are quantitatively hydrolyzed to paracetamol and corresponding 2,5-diketopiperazines at pH 7.4 and 37°C. The reactivity is increased in sarcosine and proline peptides and decreased by bulky side chains at both the N- and C-terminal residues of the dipeptide carrier. Moreover, dipeptide esters of paracetamol did not affect the levels of hepatic glutathione. Thus, dipeptides seem promising candidates as carriers for cyclization-activated prodrugs.
- Santos, Cledir,Mateus, Maria Luisa,Dos Santos, Ana Paula,Moreira, Rui,De Oliveira, Eliandre,Gomes, Paula
-
p. 1595 - 1598
(2007/10/03)
-
- SUBSTITUTED HEXAHYDROPYRROLO[1,2-A]PYRAZINES, OCTAHYDROPYRIDO[1,2-A]-PYRAZINES AND DECAHYDROPYRAZINO[1,2-A]AZEPINES
-
Novel substituted hexahydropyrrolo[1,2-a]pyrazines, octahydropyrido[1 , 2-a]-pyrazines and decahydropyrazino[1,2-a]azepines, use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds, and a method of treatment employing these compounds and compositions. The compounds show a high and selective binding affinity to the histamine H3 receptor indicating histamine H3 receptor antagonistic, inverse agonistic or agonistic activity. As a result, the compounds are useful for the treatment of diseases and disorders related to the histamine H3 receptor.
- -
-
Page/Page column 10
(2010/02/05)
-
- SUBSTITUTED HEXAHYDROPYRROLO[1,2-A]PYRAZINES, OCTAHYDROPYRIDO[1,2-A]PYRAZINES AND DECAHYDROPYRAZINO[1,2-A]AZEPINES
-
Novel substituted hexahydropyrrolo[1,2-a]pyrazines, octahydropyrido[1,2-a]-pyrazines and decahydropyrazino[1,2-a]azepines, use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds, and a method of treatment employing these compounds and compositions. The compounds show a high and selective binding affinity to the histamine H3 receptor indicating histamine H3 receptor antagonistic, inverse agonistic activity. As a result, the compounds are useful for the treatment of diseases and disorders related to the histamine H3 receptor.
- -
-
-
- Synthesis and metal complexation of chiral 3-mono- or 3,3-bis-allyl-2-hydroxypyrrolopyrazine-1,4-diones
-
A novel synthesis of chiral cyclic hydroxamic acids (4,6,8 and 10) related to cyclodipeptides is described. The crucial reduction of the nitro group of the N-nitroacetyl derivatives of (S)-α-amino acid esters is brought about by zinc-aq. ammonium chloride. The FeIII and CuII complexes of one such cyclic hydroxamic acid 10a have been prepared and their DNAse activity investigated.
- Chittari, Pabba,Jadhav, Vasant R.,Ganesh, K. Nagappa,Rajappa, Srinivasachari
-
p. 1319 - 1324
(2007/10/03)
-
- Synthesis of fused 1,2,5-triazepine-1,5-diones and some N2- and N3-substituted derivatives: Potential conformational mimetics for cis-peptidyl prolinamides
-
The synthesis of a new fused 1,2,5-triazepine-1,5-dione heterocycle, which is expected to mimic structural features of cis-peptldyl prolinamides, is described. The required parent heterocycle, corresponding to cis-glycy-(2S)-prolinamide, has been prepared in good yield by the cyclisation of N-(2-bromoacetylprolyl)-hydrazine which is itself generated in situ from the bromoacetyl proline methyl ester. Analogues corresponding to cis-(2R)-alanyl- and cis-(2S)-alanyl-(2S)-prolinamide have been similarly prepared from the appropriate N-(2-bromopropionyl)proline methyl esters and hydrazine hydrate where the cyclisation step, involving the displacement of bromide, has been shown to occur with inversion of configuration at C-2 of the propionyl moiety. Acylation at the N-3 position of the triazepine is equivalent to N-terminal acylation of the residue preceding the proline residue in cis-aminoacyl prolinamides. This has been achieved without incident using standard peptide coupling procedures. Extension at the 'C-terminal' has been achieved by preparing elaborated hydrazine precursors which are reacted with suitably activated esters of N-α-halogenoacylprolines, prior to cyclisation, to give the required fused triazepine dione. Thus it is possible to prepare constrained cis-peptidyl prolyl peptide mimetics of defined stereochemistry based upon this new triazepine dione in which all of the non-proline residues can be varied.
- Lenman, Morag M.,Lewis, Arwel,Gani, David
-
p. 2297 - 2311
(2007/10/03)
-
- Synthesis and structure of cis-peptidyl prolinamide mimetics based upon 1,2,5-triazepine-3,6-diones
-
The synthesis of novel constrained cis-peptidyl prolinamide mimetics for the dipeptide amides glycyl (2S)-prolinamide, (2S)-alanyl (2S)-prolinamide and (2R)-alanyl (2S)-prolinamide and some analogues, based upon fused 1,2,5-triazepine-3,6-diones, is described; these are suitable for elaboration into larger peptides at both the carboxy and amino termini, X-ray crystal structures for some of the compounds and intermediates are also presented.
- Lenman, Morag M.,Ingham, Scott L.,Gani, David
-
-
- Synthesis and Evaluation of Conformationally Restricted N--N-methyl-2-(1-pyrrolidinyl)ethylamines at ? Receptors. 2. Piperazines, Bicyclic Amines, Bridged Bicyclic Amines, and Miscellaneous Compounds
-
As a continuation of our earlier study (J.Med.Chem. 1992, 35, 4334-4343) we conformationally restricted the ?-receptor ligand 2-(1-pyrrolidinyl)-N--N-methylethylamine (1) by incorporating it into a series of homologous piperazines 3-9 and homopiperazines 10 and 11, diazabicyclononanes and decanes, bridgehead bicyclooctanes and nonanes as well as other miscellaneous compounds. ?-Receptor binding affinites were obtained using (+)-pentazocine in guinea pig brain membrane ?1 sites.The studies suggest that the nitrogen lone pair orient ation found in the piperazines affords the strongest binding interaction.Other nitrogen lone pair orientations or compounds representing unlikely staggered conformations of 1 -1,4-diazabicyclononane (16)> show very weak ? interaction.Comperison of the binding data of different N-substituted homologues of 1 with those of the 1--4-alkylpiperazines suggests that the two nitrogen atoms of 1 are working in opposition to one another in terms of their sensitivity to steric bulk.The high binding affinity of the 1,4-diazabicyclononanes 12 suggests that these may approximate the methyl and pyrrolidine ring conformations found in 1 when it is bound to the ? receptor.Compound 12 exhibited a 4-fold enantioselectivity favoring (+)-12.The synthesis of 6,7-dichloro-2-amino>tetralin (19) and its desmethyl derivative 20 permitted constraint of the 3,4-dichlorophenyl and N-methyl moieties of 1 into a gauche orientation.The binding data suggests that this conformation in 1 favors strong binding interaction at ?-receptors. ?-Receptor K1's ra nged from 0.55 nM for 1--4-n-butylpiperazine (7) to 654 nM for 16.Overall comparison of the results indicate that 1 is subject to considerable conformational freedom and suggests that the ?-receptor is not subject to rigid stereochemical restraints with 1.These results add to our earlier study where we restrained 1 using simple monocyclic heterocycles.
- Costa, Brian R. de,He, Xiao-shu,Linders, Joannes T.M.,Dominguez, Celia,Gu, Zi Qiang,et al.
-
p. 2311 - 2320
(2007/10/02)
-
- SYNTHETIC APPROACHES TO BREVIANAMIDES A AND B I. PREPARATION OF 4-p-METHOXYBENZYL-5-(1'-CARBOMETHOXY-2'-METHYLIDENE)-1,2-L-PYROLIDINOPIPERAZINE-3,6-DIONE VIA AN IRELAND ESTER ENOLATE CLAISEN REARRANGEMENT.
-
Using an ester enolate Claisen rearrangement to prepare 1-carbomethoxy-2-(1',1'-dimethylallyl)-2,3-dihydroindole-2-carboxylic acid followed by condensation with N-p-methoxybenzyl-glycyl-L-proline anhydride gave the title compound, a key intermediate in a synthetic approach to brevianamides A and B.
- Dunkerton, Lois V.,Chen, Hao,McKillican, Bruce P.
-
p. 2539 - 2542
(2007/10/02)
-
- Synthesis and Inhibitory Activity on Carbonic Anhydrase of Some New Sulpiride Analogues Studied by Means of a New Method
-
The pharmacological activity of several new sulpiride analogues was studied by means of a new approach, based on a potentiometric technique with a pCO2 sensor, capable of detecting carbonic anhydrase inhibition at equilibrium conditions.This procedure gives results stated as percent of inhibition of enzymatic activity (IP, inhibitory power).To prove the reliability of the proposed approach and to study structure-activity relationships, several new molecules were synthesized and tested in comparison with the two sulpiride enantiomers.A possible inhibition mechanism is discussed in terms of experimental evidence obtained from the interactions between the molecular structures of the new synthesized compounds and carbonic anhydrase.
- Botre, Claudio,Botre, Francesco,Jommi, Giancarlo,Signorini, Roberto
-
p. 1814 - 1820
(2007/10/02)
-
