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The capacity factors, k?, of 11 cyclic dipeptides (X-Y) including diastereomers have been determined on an RP-HPLC column in 30% and 50% methanol and 10%, 30%, and 50% acetonitrile solutions. These factors are roughly correlated with hydrophobic parameters, such as octanol-water partition coefficients estimated and k? values for alcohols. For a pair of diastereomers of cyclic (L-X-L-Phe) and (L-X-D-Phe) derivatives k?LL is larger than k?LD and for cyclic (D-Ala-L-Trp) and (L-Ala-L-Trp) k?LL is smaller than k?DL, particularly in highly aqueous solutions. These elution orders can be well predicted by the holistic molecular surface area approach which takes into account the folded structures of cyclic dipeptides. The present results will be useful for prediction of the log k? values of larger peptides and the hydrophobicity and related properties of peptides.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2626 – PubChem

 

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Disclosed herein, inter alia, are compounds and methods of use thereof for the modulation of CCR4 activity.

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A series of novel, highly antimicrobial salicylanilide esters of N-protected amino acids were synthesized and characterized. Their in vitro antimicrobial activity against eight fungal strains and Mycobacterium tuberculosis was determined. The compounds had the highest level of activity against Aspergillus fumigatus, Absidia corymbifera and Trichophyton mentagrophytes, and these levels were higher than that of the standard drug fluconazole. In addition, three compounds showed interesting antituberculosis activity, with inhibition ranging from 89% to 99%. (S)-4-Chloro-2-(4-trifluoromethylphenylcarbamoyl)-phenyl 2-benzyloxy-carbonylamino-propionate had the highest level of both antifungal and antimycobacterial activity. The structure-activity relationships of the new compounds are discussed.

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A stereospecific method is described for the alkylation of acyclic amino acids (alanine and phenylalanine) which proceeds with retention of configuration.The method involves a) conversion of the amino acid to the predominantly cis 2-aryl-3-carbobenzyloxy oxazolidinones (2 and 8), b) alkylation of the potassium enolate with CH3I or PhCH2Br, c) base hydrolysis and hydrogenolysis to afford the alkylated amino acid.

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Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.Read on for other articles about 20375-65-9Quality Control of 3-Phenyl-6-chloropyridazine

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The phosphotryptophan derivative l-Pro-l-Leu-l-(P)Trp(OH)2 (2b) was reported as the first example of left-hand-side1 phosphonate inhibitor of MMP-8. Its uncommon mode of binding to MMP-8 was mainly ascribed to the presence of the proline residue in P3. Ten new analogues of 2b were obtained by replacement of the aminoterminal l-Pro with aminoacid residues bearing small side chains. Most of the new analogues show an increase of affinity for MMP-2 and MMP-8, and different profiles of selectivity. Computer simulations were performed to explain the effects of substitutions on the preferred mode of binding. They reveal that most of the new analogues are probably accommodated in the right, rather than left-hand side of MMP-8 active site.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2587 – PubChem

 

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A readily available and inexpensive natural alpha -amino acid is converted into a compound represented by formula (1), which is then reacted with an organometallic reagent represented by formula (2) to give an optically active 5-hydroxyoxazolidine represented by formula (3), which is then treated with an acid to provide an optically active aminoketone represented by formula (4). The product is then converted into an optically active aminoalcohol represented by formula (5) or (6) by, for example reduction.The above process can provide an optically active aminoalcohol represented by formula (5) or (6) useful as a production intermediate for a medicine or pesticide from a readily available and inexpensive natural alpha-amino acid as a starting material stereoselectively and stably with a higher optical purity and a lower cost without racemization. This invention can also provide an optically active 5-hydroxyoxazolidine represented by formula (3) and an aminoketone represented by formula (4) as important intermediates for production of the above product as well as preparation processes therefor.

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Herein, we describe in full our investigations into the synthesis of grassypeptolide A (1) in 17 linear steps with an overall yield of 11.3 %. In particular, this work features the late-stage introduction of sensitive bis(thiazoline) heterocycles and 31-membered macrocyclization conducted at the sterically congested secondary amide site in superb conversion (72 % yield). Biological evaluation indicated that grassypeptolide A significantly inhibited cancer cell proliferation in a dose-dependent manner. It induced cancer cell apoptosis, which was associated with increased cleavage of poly(ADP-ribose) polymerase (PARP) and decreased expression of bcl-2 and bcl-xL. Furthermore, grassypeptolide A also caused cell cycle redistribution by increasing cells in the G1 phase and decreasing cells in the S and G2 phases. In addition, cell cycle arrest was correlated with downregulation of cyclin D and upregulation of p27 and p21. Cytotoxic activity: Synthesis of grassypeptolide A, an anticancer marine cyclodepsipeptide, in 17 linear steps with an overall yield of 11.3 % is described (see figure). Subsequent biological evaluation indicated that grassypeptolide A significantly inhibited cancer-cell proliferation in a dose-dependent manner. Copyright

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The invention relates to novel 2-cyanosteroids of Formula I which are useful for the induction of menses and the termination of pregnancy.

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Sep 2021 News Awesome Chemistry Experiments For 20375-65-9

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The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. To improve the potency and bioavailability of the Grb2-SH2 inhibitors, the chiral alpha-methyl-alpha-carboxyalkyl amino acid [(alpha-Me)Aa] was designed to cover dual structural and functional features separately contributed by 1-aminocyclohexanecarboxylic acid (Ac6c) and alpha-aminoadipic acid (Adi) in position Y + 1. The enantiopure L(or D)-(alpha-Me)Aa bearing various chain length carboxylalkyl side chain was conveniently synthesized by an optimized oxazolidinone methodology. The incorporation of (S)-(alpha-Me)Aa into the non-pTyr-containing peptide framework with a 5-amino acid sequence binding motif of X-2-Leu- (3?-substituted-Tyr)0-X+1-Asn really improved the inhibitory activity, affording potent (R)-sulfoxide-bridged cyclic and an open-chain series of pentapeptide inhibitors of Grb2-SH2 domain (IC50 = 1.1-5.8 muM). More significantly, these (alpha-Me)Aa incorporated peptide inhibitors showed excellent activities in inhibiting the growth of erbB2-dependent MDA-MB-453 tumor cell lines with low micromolar IC50 values, owing to the reduced peptidic nature and absence of pTyr or pTyr mimetics.

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Pyridazine – Wikipedia,
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Highly enantioselective alkylation of protected glycine diphenylmethyl (Dpm) amide 1 and Weinreb amide 10 has been realized under phase-transfer conditions by the successful utilization of designer chiral quaternary ammonium salts of type 4 as catalyst. Particularly, remarkable reactivity of the chiral ammonium enolate derived from 1b and 4c allowed the reaction with less reactive simple secondary alkyl halides with high efficiency and enantioselectivity. An additional unique feature of this chiral ammonium enolate is its ability to recognize the chirality of beta-branched primary alkyl halides, which provides impressive levels of kinetic resolution and double stereodifferentiation during the alkylation, allowing for two alpha- and gamma-stereocenters to be controlled. Combined with the subsequent reduction using LiAlH4 in cyclopentyl methyl ether (CPME), this system offers a facile access to structurally diverse optically active vicinal diamines. Furthermore, the optically active alpha-amino acid Weinreb amide 11 can be efficiently converted to the corresponding amino ketone by a simple treatment with Grignard reagents. In addition, reduction and alkylation of the optically active alpha-amino ketone into both syn and anti alpha-amino alcohols with almost complete relative and absolute stereochemical control have been achieved. With (S,S)- and (R,R)-4 in hand, the present approach renders both enantiomers of alpha-amino amides including Weinreb amides readily available with enormous structural variation and also establishes a general and practical route to vicinal diamines, alpha-amino ketones, and alpha-amino alcohols with the desired stereochemistry.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2720 – PubChem