51513-97-4Relevant articles and documents
FERROPORTIN INHIBITORS AND METHODS OF USE
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Paragraph 0199; 0200, (2020/07/07)
The subject matter described herein is directed to Ferroportin inhibitor compounds of Formula I and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds and methods of administering the compounds for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis.
A hydrochloric acid of the medicinal Starlite degradation impurity synthetic method
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Paragraph 0043-0045; 0064-0066, (2019/07/10)
The invention belongs to the technical field of pharmaceutical chemistry, and in particular relates to a hydrochloric acid of the medicinal Starlite degradation impurity synthetic method. The synthetic method, in order to N - Cbz - beta - alanine as raw m
Formamide catalyzed activation of carboxylic acids-versatile and cost-efficient amidation and esterification
Huy, Peter H.,Mbouhom, Christelle
, p. 7399 - 7406 (2019/08/20)
A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
METHOD FOR PRODUCING L-CARNOSINE DERIVATIVE AND L-CARNOSINE
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Paragraph 0093, (2019/12/05)
PROBLEM TO BE SOLVED: To provide a convenient method for producing a high-purity N-protected L-carnosine derivative and L-carnosine. SOLUTION: A production method includes reacting an acid halide (1) with an L-histidine derivative (2). (R1 and R2 are H or a protection group of an amino group; X is a halogen atom). (A TMS group is a trimethylsilyl group). SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
IMMUNOMODULATOR COMPOUNDS
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Paragraph 0221; 0222, (2018/02/28)
Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, R2a, R2b, R2c, R3, R4, R5, R6a, R6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
NEAR-INFRARED FLUORESCENT CONTRAST BIOIMAGING AGENTS AND METHODS OF USE THEREOF
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Page/Page column 116; 117, (2015/05/19)
The instant invention provides near-infrared fluorescent biological contrast agents and methods of using them.
The Synthesis of Structurally Diverse Macrocycles by Successive Ring Expansion
Kitsiou, Christiana,Hindes, Jordan J.,I'Anson, Phillip,Jackson, Paula,Wilson, Thomas C.,Daly, Eleanor K.,Felstead, Hannah R.,Hearnshaw, Peter,Unsworth, William P.
supporting information, p. 15794 - 15798 (2016/01/29)
Structurally diverse macrocycles and medium-sized rings (9-24 membered scaffolds, 22 examples) can be generated through a telescoped acylation/ring-expansion sequence, leading to the insertion of linear fragments into cyclic β-ketoesters without performin
Macrocyclic pyridyl polyoxazoles: Structure-activity studies of the aminoalkyl side-chain on G-quadruplex stabilization and cytotoxic activity
Blankson, Gifty,Rzuczek, Suzanne G.,Bishop, Cody,Pilch, Daniel S.,Liu, Angela,Liu, Leroy,LaVoie, Edmond J.,Rice, Joseph E.
, p. 11938 - 11963 (2013/11/06)
Pyridyl polyoxazoles are 24-membered macrocyclic lactams comprised of a pyridine, four oxazoles and a phenyl ring. A derivative having a 2-(dimethylamino)ethyl chain attached to the 5-position of the phenyl ring was recently identified as a selective G-quadruplex stabilizer with excellent cytotoxic activity, and good in vivo anticancer activity against a human breast cancer xenograft in mice. Here we detail the synthesis of eight new dimethylamino-substituted pyridyl polyoxazoles in which the point of attachment to the macrocycle, as well as the distance between the amine and the macrocycle are varied. Each compound was evaluated for selective G-quadruplex stabilization and cytotoxic activity. The more active analogs have the amine either directly attached to, or separated from the phenyl ring by two methylene groups. There is a correlation between those macrocycles that are effective ligands for the stabilization of G-quadruplex DNA (ΔTtran 15.5-24.6 °C) and cytotoxicity as observed in the human tumor cell lines, RPMI 8402 (IC 50 0.06-0.50 μM) and KB3-1 (IC50 0.03-0.07 μM). These are highly selective G-quadruplex stabilizers, which should prove especially useful for evaluating both in vitro and in vivo mechanism(s) of biological activity associated with G-quaqdruplex ligands.
Design, Synthesis, ADME Properties, and Pharmacological Activities of β-Alanyl-D-histidine (D-Carnosine) Prodrugs with Improved Bioavailability
Orioli, Marica,Vistoli, Giulio,Regazzoni, Luca,Pedretti, Alessandro,Lapolla, Annunziata,Rossoni, Giuseppe,Canevotti, Renato,Gamberoni, Luca,Previtali, Massimo,Carini, Marina,Aldini, Giancarlo
experimental part, p. 1269 - 1282 (2012/05/20)
β-Alanyl-D-histidine (D-CAR, the enantiomer of the natural dipeptide carnosine) is a selective and potent sequestering agent of reactive carbonyl species (RCS) that is stable against carnosinase, but is poorly absorbed in the gastrointestinal tract. Herein we report a drug discovery approach aimed at increasing the oral bioavailability of D-CAR. In our study we designed, synthesized, and evaluated a series of novel lipophilic D-CAR prodrugs. The considered prodrugs can be divided into two categories: 1)derivatives with both terminal groups modified, in which the carboxyl terminus is always esterified while the amino terminus is protected by an amidic (N-acetyl derivatives) or a carbamate (ethyloxy or benzyloxy derivatives) function; 2)derivatives with only one terminus modified, which can be alkyl esters as well as amidic or carbamate derivatives. The prodrugs were designed considering their expected lipophilicity and their hydrolysis predicted by docking simulations on the most important human carboxylesterase (hCES1). The stability and metabolic profile of the prodrugs were studied by incubating them with rat and human serum and liver fractions. The octyl ester of D-CAR (compound 13) was chosen as a candidate for further pharmacological studies due to its rapid hydrolysis to the bioactive metabolite invitro. Pharmacokinetic studies in rats confirmed the invitro data and demonstrated that the oral bioavailability of D-CAR is increased 2.6-fold if given as an octyl ester relative to D-CAR. Compound 13 was then found to dose-dependently (at daily doses of 3 and 30mgkg-1 equivalent of D-CAR) decrease the development of hypertension and dyslipidemia, to restore renal functions of Zucker fa/fa obese rats, and to inhibit the carbonylation process (AGEs and pentosidine) as well as oxidative stress (urinary 8-epi-prostaglandin F2α and nitrotyrosine). A plausible mechanism underlying the protective effects of 13 is RCS sequestration, as evidenced by the significant increase in the level of adduct between CAR and 4-hydroxy-trans-2-nonenal (HNE, the main RCS generated by lipid oxidation) in the urine of treated animals. The modest oral absorption of D-carnosine (D-CAR), a bioactive compound able to detoxify reactive carbonyl species, prompted us to design, synthesize, and evaluate new lipophilic D-CAR prodrugs. Among these, D-CAR with an octyl ester has greater oral bioavailability than D-CAR, as demonstrated by pharmacokinetic studies. The new compound reduces the development of hypertension and dyslipidemia, and restores renal function in Zucker fa/fa obese rats.
VIGABATRIN BIOISOTERES AND RELATED METHODS OF USE
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Page/Page column 6; 11-12, (2010/11/26)
Compounds bioisoteric to vigabatrin and related methods of use.
