Ring closure reactions of methyl N‐(haloacetyl)anthranilates with ammonia

Abstract

In the presence of ammonia, methyl N‐(bromoacetyl)anthranilate (4) is cyclized into 3H‐1,4‐benzodiaze‐pine‐2,5(1H,4H)‐dione (1). However, when 4 is replaced with methyl N‐(chloroacetyl)anthranilate (6), the only heterocyclic product formed in the reaction is 2‐(chloromethyl)quinazoline‐4(3H)‐one (7). Under analogous conditions, 3‐haloacetamidocrotonates (9, 10) do not yield any heterocyclic products and no 1,4‐diazepines can be obtained.

Synthesis and In Vitro Evaluation of Bis‐intercalators with Varied Linkers between Aminochloropyrimidine Rings

“…The first group of aminochloropyrimidine bis-intercalators, N,N 0 -bis(2-amino-6-chloro-4-pyrimidyl)-1,8-diamino-3,6dioxaoctane (10), N,N 0 -bis(2-amino-6-chloro-4-pyrimidyl)-1,10-diamino-4,7-dioxadecane (11), N,N 0 -bis(2-amino-6chloro-4-pyrimidyl)-1,12-diamino-4,9-dioxadodecane (12), and N,N 0 -bis(2-amino-6-chloro-4-pyrimidyl)-1,13-diamino-4,7,10-trioxatridecane (13), were prepared by nucleophilic substitution of 2-amino-4,6-dichloropyrimidine (1) with the appropriate polyether diamines (9): 1,8-diamino-3,6-dioxaoctane, 1,10-diamino-4,7-dioxadecane, 1,12-diamino-4,9dioxadodecane, and 1,13-diamino-4,7,10-trioxatridecane, respectively, in the presence of triethylamine by refluxing in 1-butanol (Scheme 2). On the basis of our experimental data, this series of reactions gives yields from 78 to 89%.…”

“…The anticancer activity of the new bis-intercalators (10)(11)(12)(13)(15)(16)(17)(18)(19) was tested in vitro by determining cytotoxicity against a series of cell lines: P388 murine leukemia cells, PANC-1 human pancreatic cancer cells, A549 non-small cell lung adenocarcinoma cells, DLD-1 human colon cancer cells, and NCI/ADR drug-resistant human breast cancer cells. The anticancer activity of the new bis-intercalators (10)(11)(12)(13)(15)(16)(17)(18)(19) was tested in vitro by determining cytotoxicity against a series of cell lines: P388 murine leukemia cells, PANC-1 human pancreatic cancer cells, A549 non-small cell lung adenocarcinoma cells, DLD-1 human colon cancer cells, and NCI/ADR drug-resistant human breast cancer cells.…”

“…DNA intercalators are organic molecules with planar aromatic ring systems that can bind to the DNA double helical structures resulting in distortion of the DNA backbone conformation and interference with DNA-protein interaction [1][2][3][4]. Within the framework of our systematic studies of novel heterocyclic compounds with potential biological activity [5][6][7][8][9][10][11][12][13][14][15], we have synthesized two additional series of bisaminochloropyrimidine compounds bridged with different lipophilicity or limited flexibility of linkers as potential DNA intercalators. Some of them are currently used as chemotherapeutic agents for solid or non-solid malignant tumors [1].…”

“…The lipophilic linkers in the synthesized bis-intercalators are represented by alternating methylene groups and oxygen atoms in a chain, with a pyrimidine ring containing an amino group and a chloro group at each end (10)(11)(12)(13). The lipophilic linkers in the synthesized bis-intercalators are represented by alternating methylene groups and oxygen atoms in a chain, with a pyrimidine ring containing an amino group and a chloro group at each end (10)(11)(12)(13).…”

Synthesis of 2,5‐Diketopiperazine Derivatives Using 2‐Isocyanophenyl 4‐Methylbenzoate as a Fragrant Convertible Isocyanide

“…Many diketopiperazine derivatives are among the most important backbones in modern drug discovery industries. The compounds containing these core templates have widespread biological applications, such as being utilized as antagonists of the platelet glycoprotein IIb/IIa , anticonvulsant agents , serine protease inhibitors , and CNS agents . In addition, the diketopiperazine scaffold often occurs in complex nature products .…”