Éthyl 5‐méthylthio‐3‐(4‐nitrophényl)‐3a‐phényl‐3a,4‐dihydro‐3H‐[1,2,4]­triazolo[4,3‐a][1,5]benzodiazépine‐1‐carboxylate

Condensation of N‐p‐nitrophenyl‐C‐ethoxycarbonylnitril­im­ine with 2‐methylthio‐4‐phenyl‐3H‐1,5‐benzodiazepine leads to the title compound, C₂₆H₂₃N₅O₄S. It has been established that 1,3‐dipolar cycloaddition occurs on the C4 =N5 double bond of the 1,5‐benzodiazepine.     

11‐Methyl‐12a‐phenyl‐9a,12a‐dihydrophenanthro[9′,10′:5,6][1,4]dioxino[2,3‐d]oxazole and 9a‐(10‐hydroxyphenanthren‐9‐yl)‐11,12a‐diphenyl‐9a,12a‐dihydrophenanthro[9′,10′:5,6][1,4]dioxino[2,3‐d]oxazole

In the title compounds, C₂₄H₁₇NO₃, (I), and C₄₃H₂₇NO₅, (II), the dioxine ring is not planar and tends toward a boat conformation. The oxazoline ring adopts a twisted conformation in mol­ecule (I) but is essentially planar in mol­ecule (II). The configuration of the dioxine–oxazoline system is determined by the sp³ state of the two shared atoms. The phenanthrene moiety is nearly coplanar with the dioxine ring, while the phenyl ring is perpendicular to the attached oxazole ring. The triclinic unit cell of (II) contains two crystallographically independent mol­ecules related by a pseudo‐inversion centre.     

Synthesis of new thieno[2,3‐d]pyrimidines,thieno[3,2‐e]pyridines,and thieno[2,3‐d][1,3]oxazines

o‐Aminothiophene dicarbonitrile 1 on neat reaction with cyclic ketones in anhydrous ZnCl₂ yielded mixture of fused aminopyridine 3 and iminospirooxazine 4 derivatives. Similarly, pyrimidine derivatives 5 and 8 were obtained by the reaction of this intermediate 1 with formic acid and DMF‐DMA followed by hydrazine hydrate, respectively. The reaction of o‐amino‐thiophene dicarboxamide 2 at ambient temperature with cyclic ketones yielded spiropyrimidine 10 as a sole product in quantitative yield. The regioselective anellated pyrimidine 9 , 11 , and dihydropyrimidine 12 derivatives were also obtained by the reaction with aromatic aldehydes in presence of piperidine and iodine respectively. J. Heterocyclic Chem., (2012).     

11‐Methyl‐12a‐phenyl‐9a,12a‐di­hydro­phenanthro­[9′,10:5,6][1,4]­dioxino­[2,3‐d]­thia­zole

In the title compound, C₂₄H₁₇NO₂S, the dioxine and thia­zoline rings are distorted from planarity towards a half‐chair and an envelope conformation, respectively. The configurations of the dioxine ring, the thiazoline ring and the attached phenyl ring are conditioned by the sp³ state of the two bridgehead C atoms. The phenanthrene system is nearly coplanar with the dioxine ring, while the attached phenyl ring is orthogonal to the thia­zoline ring.     

Synthesis of [1,4]benzodioxino[2,3‐c and 2,3‐d]pyridazinones

Reaction of chloropyridazin‐3‐one 1, 5 and 10 with catechol in the presence of potassium carbonate gave the corresponding [1,4]benzodioxino[2,3‐e and/or 2,3‐d]pyridazinones 2, 7, 8 and 11 .     

Synthesis and antimalarial activity of ethyl 3‐amino‐4‐oxo‐9‐(phenylsubstituted)thieno[2,3‐b]quinoline‐2‐carboxylate derivatives

A series of thieno[ 2 ,3‐b]quinolone derivatives were synthesized and investigated for their abilities to inhibit β‐hematin formation, hemoglobin hydrolysis and in vivo for their efficacy in rodent Plasmodium berghei. Compound 3b was the most promising as inhibitor of hemoglobin hydrolysis, and its effects as inhibitor of β‐hematin formation was promising. When the aromatic ring was substituted in 2 (Me), in 3 (CF₃) or in 2,4 (Cl) the inhibition of hemoglobin proteolysis was maximal (88%), the rest of compounds maintained a low inhibition. The most active compound to emerge in vitro and in murine studies, was 3b suggesting an antimalarial activity via multiple mechanisms.     

Syntheses of substituted pyrrolo[2,3‐d]imidazole‐5‐carboxylates and substitued pyrrolo[3,2‐d]imidazole‐5‐carboxylates

Starting from readily available p‐substituted‐benzylamines a series of ethyl 2‐alkylthio‐1‐substituted‐ben‐zylpyrrolo[2,3‐d]imidazole‐5‐carboxylates was prepared. In addition, starting from 2‐alkyl‐4(or 5)‐formylimidazoles and methyl 4′‐bromomethylbiphenyl‐2‐carboxylate a series of methyl substituted‐pyrrolo[2,3‐d]imidazole‐5‐carboxylates and methyl substituted‐pyrrolo[3,2‐d]imidazole‐5‐carboxylates was prepared.     

Synthesis of tricyclic pyrido[2,3‐b][1,4]‐thiazines via nucleophilic substitution of activated precursors

Pyrido‐anellated compounds analogous to tricyclic 1,4‐benzothiazine derivatives were synthesized. Thus, under mild reaction conditiones substitution of thiolactim 3 with different N‐nucleophiles yielded the precursors for compounds, which were cyclized in a further step to the corresponding tricyclic derivatives.     

Facile Synthesis of Naphtho[2,3‐d]thiazoles,Naphtho[2,3‐e][1,3,4]thiadiazines and Bis(naphtho[2,3‐d]thiazolyl)copper(II) Derivatives from Heteroylthiosemicarbazides

A one step synthesis protocol for the conversion of heteroylthiosemicarbazides and 2,3‐dichloro‐1,4‐naphthoquinone to naphtho[2,3‐d]thiazoles, naphtho[2,3‐e][1,3,4]thiadiazines as well as bis(naphtho[2,3‐d]thiazolyl)copper(II) derivatives is described. The products were conclusively confirmed by single crystal X‐ray analyses. A mechanism for the formation of the products is presented.     

Synthesis of Some Novel Pyrido[2,3‐d]pyrimidine and Pyrido[3,2‐e][1,3,4]triazolo and Tetrazolo[1,5‐c]pyrimidine Derivatives as Potential Antimicrobial and Anticancer Agents

A novel series of pyrido[2,3‐d]pyrimidines 3a – d , 4a – d , 5a – d , 6a – d , and 7a – d ; pyrido[3,2‐e][1,3,4]triazolo; and tetrazolo[1,5‐c]pyrimidines 10a – d and 11a – d was synthesized through different chemical reactions starting from 2‐amino‐3‐cyano‐4,6‐diarylpyridines. The newly synthesized heterocycles were characterized by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral data. Compounds have been screened for their antibacterial and antifungal activities. The data showed that the presence of electron‐donating group such as p‐methoxyphenyl increases the antimicrobial activity. Also, the compounds have shown anticancer activity for colon and liver cancer cells.     

Synthesis and Anticancer Evaluation of Some Novel Thiophene,Thieno[3,2‐d]pyrimidine,Thieno[3,2‐b]pyridine,and Thieno[3,2‐e][1,4]oxazepine Derivatives Containing Benzothiazole Moiety

In an attempt to establish novel candidate with promising anticancer activity, two derivatives of (benzo[d]thiazol‐2‐yl)thiophene backbone 1 and 14 were synthesized, and they further reacted with various chemical reagents to afford the corresponding substituted thiophene derivatives 6 , 8 , 10 , 15 , 17 , and 20 , thieno[3,2‐d]pyrimidine derivatives 2 – 5 , 7 , 9 , 16 , 21 , 23 , and 24 , thieno[3,2‐b]pyridine derivatives 11 – 13 , and thieno[3,2‐e][1,4]oxazepine derivative 18 . Structures of prepared compounds were affirmed via spectral and elemental data. Among the obtained compounds, seven derivatives 2 , 3 , 4 , 5 , 11 , 12 , and 13 were chosen by National Cancer Institute, USA. Such compounds were screened for their antitumor activity versus 60 cancer cell lines in one‐dose (10 μmol) screening assay. The outcomes showed that all selected compounds exhibited moderate to high anticancer activity towards many cancer cell lines among which compounds 5 and 11 exerted potent antitumor activity against numerous malignant growth cell lines particularly Ovarian Cancer IGROV1.     

5‐Phenyl‐9H‐1,3‐dioxolo[4,5‐h][2,3]benzodiazepin‐8(7H)‐one

The title compound, C₁₆H₁₂N₂O₃, is a novel potent and selective non‐competitive antagonist at AMPA/kainate receptors [AMPA is 2‐amino‐3‐(3‐hydroxy‐5‐methylisoxazol‐4‐yl)­propionic acid and kainate is 3‐carboxy­methyl‐4‐isopropenyl­pyrrolidine‐2‐carboxylic acid]. The crystal structure has been determined at room temperature by X‐ray diffraction and the seven‐membered ring shows the usual boat conformation. The energy stabilization of the crystal packing of the title compound by significant hydrogen‐bond inter­actions is discussed using theoretical computations.     

Novel Benzothiazine Derivatives via Formylation of 2,3‐Dihydro‐4H‐benzo[e][1,4]thiazin‐3‐on‐1,1‐dioxide

A simple, efficient, and clean protocol for the formylation of 2,3‐dihydro‐4H‐1,4‐benzo[e][1,4]thiazin‐3‐on‐1,1‐dioxide is developed. Novel benzothiazine derivatives are synthesized by the reactions of aminovinyl derivative 6 and carbaldehyde 7 with nucleophiles.     

The crystal structure of 9‐chloro‐4,5‐dihydro‐2‐ethyl‐1‐(2,4,6‐trichlorophenyl)‐1H‐1,2,4‐triazolo[3,2‐d][1,5]‐benzoxazepinium hexachloroantimonate

The title compound 4 , i.e. 9‐chloro‐4,5‐dihydro‐2‐ethyl‐1‐(2,4,6‐trichlorophenyl)‐1H‐1,2,4‐triazolo[3,2‐d]‐[1,5]benzoxazepinium hexachloroantimonate, is a novel 6‐7‐5 tricyclic heterocycle. C₁₈H₁₄Cl₄N₃O·SbCJ₆, M = 764.61, P2₁/c(#14), a = 13.457(4), b = 11.583(2), c = 18.992(3) Å α = 90, β = 110.11(1)°, Z = 4, V = 2780(1) ų, D_c = 1.827 g/cc, μ (MoKα) = 19.69 cm^?1, F(000) = 1488.00, T = 293 K, R_int = 0.055 for 3094 independent reflections with I>3.00σ(I). The five‐membered heterocyclic ring is nearly planar, with the trichlorophenyl ring at N(2) almost perpendicular to it. However, the seven‐membered ring is not planar, but adopts a twist‐boat conformation.     

Synthesis of novel,nonclassical 2‐amino‐4‐oxo‐6‐(arylthio)ethylpyrrolo[2,3‐d] pyrimidines as potential inhibitors of thymidylate synthase

A novel series of 14 nonclassical 6‐substituted pyrrolo[2,3‐d]pyrimidines 2a ‐ 2n were designed as potential inhibitors of thymidylate synthase, based on previously reported 2‐amino‐4‐oxopyrrolo[2,3‐d]‐pyrimidines 1a and 1b . The synthesis of the target compounds 2a‐2n was accomplished by nucleophilic displacement of the mesylate 11 with appropriately substituted aromatic thiols. Most of the target compounds did not show inhibition of either Escherichia coli thymidylate synthase or recombinant human thymidylate synthase at the concentrations tested. However, compounds 2h (2,4‐dichloro), 2j (3,4‐dichloro) and 2m (4‐nitro) did show 25%, 40% and 35% inhibition of human thymidylate synthase at 23 μM, 23 μM and 24 μM, respectively. These observations are in accordance with previous reports, which suggest that strong electron withdrawing substituents on the side chain aromatic ring are conducive to inhibition of thymidylate synthase.