New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• the occurrence of these ring systems in various biologically important compounds (Figure 1). A number of 3,4-dihydroquinazolines were found to show remarkable anticancer [1], antiviral [2], antidepressant [3], antifungal [4], selective somatostatin 2 (ss2) agonistical [5], β-site amyloid precursor

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• . Small peptides that recognize target receptors on tumor cells might be suitable targeting moieties for this purpose. Hormone peptides, in particular, GnRH and somatostatin derivatives that possess antiproliferative effect on their own, are among the best candidates as homing peptides [10]. A.V. Schally

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• lysine contains a free amine group (εNH2) allowing orthogonal coupling with a cytotoxic warhead [19]. A considerable number of PDCs based on GnRH [59][60][61][62][63] exist and our group has exploited this peptide to construct two PDCs [18][19]. Somatostatin (SST): Somatostatin is a neuropeptide produced

• by neuroendocrine, inflammatory and immune cells and has an important role in various physiological functions acting as a classical endocrine hormone, a paracrine regulator or a neurotransmitter [64]. Somatostatin appears in two distinct active forms: somatostatin-14 (SST-14) and somatostatin-28 (SST

• -28). Both SST-14 and SST-28 exhibit biological activity through high-affinity membrane receptors (somatostatin receptor 1–5; SSTR1–5), that are widely distributed throughout the human body in various tissues like the nervous, pituitary, kidney, lung and immune cells [65][66]. SSTRs are overexpressed

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• (e.g., somatostatin-14, bombesin) could not inhibit the receptor binding at concentrations up to 1 µM [51][52]. Comparing our results with these findings from literature we can assume that the analyzed GnRH-III–Dau conjugates bind to the GnRH-receptor in a specific manner. However, the binding affinity

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• proved highly efficient in solid-phase synthesis of a somatostatin analogue bearing three Nα-methylation sites that could not be synthesized using the previously described state-of-the-art methods. Keywords: N-methylation; nucleophilic addition; solid phase; somatostatin; sulfonylation; Introduction

• for the synthesis of multiple-sites methylated peptide that could not be synthesized using the state-of-the-art strategies. Results and Discussion The backbone precyclic somatostatin Nα-methylated analogue, peptide 1SW-1 (Figure 2), possesses three methylation sites on three different amino acids in

• optimization of the N-methylation process. i) Introduction of the o-NBS group to amines 1–5 using o-NBS-Cl. ii) Methylation of sulfonylamides 1a–5a using (Me)2SO4. iii) Removal of the o-NBS group using 2-mercaptoethanol to give methylated 1c–5c. 1SW-1 is a multiple sites N-methylated analogue of somatostatin

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• adenovirus coat for vaccine development [5], antibodies or antibody fragments to prolong their circulating half-lives in vivo [6] and selective alkylation and acylation of amino groups in a somatostatin analog using two different PEG reagents [7]. Also, PEGylation of low molecular weight drugs in order to

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• -NH2 was found to bind to a human somatostatin receptor with nanomolar affinity [7][8][9]. Despite their interesting properties, β2-amino acids in particular occur only rarely in nature. Several peptidic natural products contain 3-amino-2-methylpropionic acid (β2-homoalanine) as a building block [10