1628-29-1Relevant articles and documents
Potential CNS antitumor agents - phenothiazines I: Nitrogen mustard derivatives
Hirata,Driscoll
, p. 1699 - 1701 (1976)
Four phenothiazine derivatives containing the bis (β chloroethyl) aminopropyl side chain were prepared and evaluated in the murine L 1210, P 388 and B 16 melanoma intraperitoneal tumor systems. Moderate P 388 activity was observed. An aminoethyl phenothiazine mustard was compared with the aminopropyl analogs and was superior in all test systems. None of the compounds tested against the murine ependymoblastoma brain tumor system was active.
Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs
Chan, Cecil,Yin, Hong,Garforth, Jacqui,McKie, James H.,Jaouhari, Rabih,Speers, Peter,Douglas, Kenneth T.,Rock, Peter J.,Yardley, Vanessa,Croft, Simon L.,Fairlamb, Alan H.
, p. 148 - 156 (1998)
Given the role of trypanothione in the redox defenses of pathogenic trypanosomal and leishmanial parasites, in contrast to glutathione for their mammalian hosts, selective inhibitors of trypanothione reductase are potential drug leads against trypanosomiasis and leishmaniasis. In the present study, the rational drug design approach was used to discover tricyclic neuroleptic molecular frameworks as lead structures for the development of inhibitors, selective for trypanothione reductase over host glutathione reductase. From a homology-modeled structure for trypanothione reductase, replaced in the later stages of the study by the X-ray coordinates for the enzyme from Crithidia fasciculata, a series of inhibitors based on phenothiazine was designed. These were shown to be reversible inhibitors of trypanothione reductase from Trypanosoma cruzi, linearly competitive with trypanothione as substrate and noncompetitive with NADPH, consistent with ping-pong bi bi kinetics. Analogues, synthesized to define structure-activity relationships for the active site, included N-acylpromazines, 2-substituted phenothiazines, and trisubstituted promazines. Analysis of K(i) and I50 data, on the basis of calculated log P and molar refractivity values, provided evidence of a specially favored fit of small 2-substituents (especially 2-chloro and 2-trifluoromethyl), with a remote hydrophobic patch on the enzyme accessible for larger, hydrophobic 2-substituents. There was also evidence of an additional hydrophobic enzymic region available to suitable N-substituents of the promazine nucleus. K(i) data also indicated that the phenothiazine nucleus can adopt more than one inhibitory orientation in its binding site. Selected compounds were tested for in vitro activity against Trypanosoma brucei, T. cruzi, and Leishmania donovani, with selective activities in the micromolar range being determined for a number of them.
A ONE-STEP SYNTHESIS OF 2,3-DIHYDRO-1,4-BENZOTHIAZINES AND PHENOTHIAZINES FROM 1,3-THIAZOLIDINE DERIVATIVES OF CYCLOHEXANONES
Caputo, Romualdo,Ferreri, Carla,Longobardo, Luigi,Mastroianni, Domenico,Palumbo, Giovanni,Pedatella, Silvana
, p. 1641 - 1644 (1993)
N-Acetyl-1,3-thiazolidine derivatives of cyclohexanones, when treated with a threefold excess N-bromosuccinimide in anhydrous chloroform at room temperature, smoothly afford N-acetyl-2,3-dihydro-1,4-benzothiazines.This represents the first general route to such heterocyclic system in one step from aliphatic precursors.The synthesis optically active N-acetyl-2,3-dihydro-1,4-benzothiazines is also reported.
Structure-activity relationships for inhibition of human cholinesterases by alkyl amide phenothiazine derivatives
Darvesh, Sultan,McDonald, Robert S.,Penwell, Andrea,Conrad, Sarah,Darvesh, Katherine V.,Mataija, Diane,Gomez, Geraldine,Caines, Angela,Walsh, Ryan,Martin, Earl
, p. 211 - 222 (2005)
A number of phenothiazine N-alkyl amide derivatives were synthesized in order to examine the structure-activity relationships for inhibition of human acetylcholinesterase and butyrylcholinesterase. Several lines of evidence indicate that inhibition of butyrylcholinesterase (BuChE) is important in the treatment of certain dementias. Further testing of this concept requires inhibitors that are both BuChE-selective and robust. N-alkyl derivatives (2, 3, 4) of phenothiazine (1) have previously been found to inhibit only BuChE in a mechanism involving π-π interaction between the phenothiazine tricyclic ring system and aromatic residues in the active site gorge. To explore features of phenothiazines that affect the selectivity and potency of BuChE inhibition, a series of N-carbonyl derivatives (5-25) was synthesized and examined for the ability to inhibit cholinesterases. Some of the synthesized derivatives also inhibited AChE through a different mechanism involving carbonyl interaction within the active site gorge. Binding of these derivatives takes place within the gorge, since this inhibition disappears when the molecular volume of the derivative exceeds the estimated active site gorge volume of this enzyme. In contrast, BuChE, with a much larger active site gorge, exhibited inhibition that increased directly with the molecular volumes of the derivatives. This study describes two distinct mechanisms for binding phenothiazine amide derivatives to BuChE and AChE. Molecular volume was found to be an important parameter for BuChE-specific inhibition.
Utilizing d–pπ Bonds for Ultralong Organic Phosphorescence
Tian, Shuai,Ma, Huili,Wang, Xuan,Lv, Anqi,Shi, Huifang,Geng, Yun,Li, Jie,Liang, Fushun,Su, Zhong-Min,An, Zhongfu,Huang, Wei
supporting information, p. 6645 - 6649 (2019/04/04)
Developing pure organic materials with ultralong lifetimes is attractive but challenging. Here we report a concise chemical approach to regulate the electronic configuration for phosphorescence enhancement. After the introduction of d–pπ bonds into a phenothiazine model system, a phosphorescence lifetime enhancement of up to 19 times was observed for DOPPMO, compared to the reference PPMO. A record phosphorescence lifetime of up to 876 ms was obtained in phosphorescent phenothiazine. Theoretical calculations and single-crystal analysis reveal that the d–pπ bond not only reduces the (n, π*) proportion of the T1 state, but also endows the rigid molecular environment with multiple intermolecular interactions, thus enabling long-lived phosphorescence. This finding makes a valuable contribution to the prolongation of phosphorescence lifetimes and the extension of the scope of phosphorescent materials.
Synthesis and microbiological evaluation of some new phenothiazine derivatives
Sen, Sandip,De, Biplab,Mallik, Arunabha,Roy, Biswabara,Kumar, Deepak
, p. 221 - 226 (2018/09/14)
A new series of 4-(10-acetyl-10H-phenothiazine-3-yl)-1-phenylazetidine-2-ones (6a-g) was prepared by intermolecular cyclization of Schiff bases (5a-g) and chloroacetyl chloride in the presence of base catalyst triethylamine. The microbiological evaluations of the compounds 6a-g were performed, and the compounds 6a, 6b, 6d, 6f, and 6g showed significant antimicrobial activities.
