70638-56-1

Upstream product

• 104-88-1 4-chlorobenzaldehyde 
• 17356-08-0 thiourea 
• 105-56-6 ethyl 2-cyanoacetate 

Downstream Products

• 109532-69-6 7-(4-chlorophenyl)-2,3-dihydro-5-oxo-5H-thiazolo<3,2-a>pyrimidine-6-carbonitrile 
• 109532-70-9 8-(4-chlorophenyl)-3,4-dihydro-6-oxo-5H-thiazolo<3,2-a>pyrimidine-7-carbonitrile 
• 109532-80-1 6-(4-chlorophenyl)-3,4-dihydro-3-(4-nitrobenzyl)-2-(4-nitrobenzylthio)-4-oxo-5-pyrimidinecarbonitrile 
• 145434-80-6 3-amino-7-(4-chlorophenyl)-5H-5-oxo-thiazolo<3,2-a>pyrimidine-2,6-dicarbonitrile 
• 132968-15-1 2-(7-Chloro-4-methyl-5-oxo-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinazolin-1-ylmethylsulfanyl)-4-(4-chloro-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 
• 109552-71-8 1-methyl-2-(methylthio)-6-oxo-4-(4-chlorophenyl)-1,6-dihydropyrimidine-5-carbonitrile 
• 128061-80-3 4-(4-chlorophenyl)-2-(methylsulfanyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 
• 191659-59-3 Acetic acid (2R,3R,4S,5R,6R)-4,5-diacetoxy-6-acetoxymethyl-2-[4-(4-chloro-phenyl)-5-cyano-6-oxo-2-((2S,3R,4S,5R,6R)-3,4,5-triacetoxy-6-acetoxymethyl-tetrahydro-pyran-2-ylsulfanyl)-6H-pyrimidin-1-yl]-tetrahydro-pyran-3-yl ester 
• 191659-46-8 Acetic acid (2R,3R,4S,5S,6R)-4,5-diacetoxy-6-acetoxymethyl-2-[4-(4-chloro-phenyl)-5-cyano-6-oxo-2-((2S,3R,4S,5S,6R)-3,4,5-triacetoxy-6-acetoxymethyl-tetrahydro-pyran-2-ylsulfanyl)-6H-pyrimidin-1-yl]-tetrahydro-pyran-3-yl ester 
• 109532-77-6 4-(4-Chloro-phenyl)-1-ethyl-2-ethylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 
• 109532-78-7 4-(4-Chloro-phenyl)-6-oxo-1-propyl-2-propylsulfanyl-1,6-dihydro-pyrimidine-5-carbonitrile 
• 109532-79-8 1-Benzyl-2-benzylsulfanyl-4-(4-chloro-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 
• 145434-83-9 7-(4-chlorophenyl)-4,9-dioxo-1H,4H,9H-thiazolo<3,2-a:4,5-d'>dipyrimidine-8-carbonitrile 
• 145434-90-8 3-Amino-1-benzyl-7-(4-chloro-phenyl)-5-oxo-1,5-dihydro-imidazo[1,2-a]pyrimidine-6-carbonitrile 

Relevant academic research and scientific papers

Design, synthesis and in vitro evaluation of 4-oxo-6-substituted phenyl-2-thioxo1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives as HIV integrase strand transfer inhibitors

Aim: To design, synthesis and in vitro evaluation of 4-oxo-6-substituted phenyl-2-thioxo1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives as HIV integrase strand transfer inhibitors. Background: Human immunodeficiency virus-1 (HIV-1), a member of retroviridae family, is the primary causative agent of acquired immunodeficiency syndrome (AIDS). Three enzymes viz: inte-grase (IN), reverse transcriptase (RT) and protease play important role in its replication cycle. HIV-1 integrase is responsible for the incorporation of viral DNA into human chromosomal DNA by cata-lyzing two independent reactions, 3′-processing (3′-P) and strand transfer (ST), which are observed as the “point of no-return” in HIV infection. Objective: To develop inhibitors against HIV integrase strand transfer step. Methods: Our previous results indicated that tetrahydro pyrimidine-5-carboxamide derivatives are potent HIV-1 IN inhibitors (unpublished results from our laboratory). Taking clue from above studies and our own experience, we hypothesized 4-oxo-6-substituted phenyl-2-thioxo1,2,3,4-tetrahydropyrimidine-5-carbonitrile analogues (14a to 14n) as inhibitors of HIV-1 Integrase strand transfer. Prototype compound 14 can be viewed as hybrid structure having characteristics of dihy-dropyrimidine derivatives 10-12 and tyrphostin 13. Results: A total of fourteen derivatives of 4-oxo-6-substituted phenyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (14a-14n) were synthesized and evaluated using HIV-1 Integrase Assay Kit (Xpressbio Life Science Products, USA). The percentage inhibition of all compounds was investigated at 10 μM concentration and IC50 value of few highly active compounds was studied. The obtained results were validated by in silico molecular docking study using Glide (maestro version 9.3, Schr?dinger suite) in extra precision (XP) mode. Conclusion: Fourteen 4-oxo-6-substituted phenyl-2-thioxo 1,2,3,4-tetrahydropyrimidine-5-carbonitrile analogues were synthesized and evaluated for HIV-1 IN inhibitory activity. Three compounds 14a, 14e, and 14h exhibited significant percentage inhibition of HIV-1 IN. There was good in vitro-in silico correlation. However, none of the derivative was active against HIV-1 and HIV-2 below their cytotoxic concentration. It needs to be seen whether these compounds can be explored further for their anti-HIV or cytotoxic potential.

Design and synthesis of pyrimidine-5-carbonitrile hybrids as COX-2 inhibitors: Anti-inflammatory activity, ulcerogenic liability, histopathological and docking studies

Two new series of 1,3,4-oxadiazole and coumarin derivatives based on pyrimidine-5-carbonitrile scaffold have been synthesized and evaluated for their COX-1/COX-2 inhibitory activity. Compounds 10c, 10e, 10h-j, 14e-f, 14i and 16 were found to be the most potent and selective inhibitors of COX-2 (IC50 0.041–0.081 μM, SI 139.74–321.95). Eight compounds were further investigated for their in vivo anti-inflammatory activity. The most active derivatives 10c, 10j and 14e displayed superior in vivo anti-inflammatory activity (% edema inhibition 39.3–48.3, 1 h; 58.4–60.5, 2 h; 70.8–83.2, 3 h; 78.9–89.5, 4 h) to the reference drug celecoxib (% edema inhibition 38.0, 1 h; 48.8, 2 h; 58.4, 3 h; 65.4, 4 h). These derivatives were also tested for their ulcerogenic liability, compound 10j showed better safety profile with reference to celecoxib while 10c and 14e exhibited mild lesions. Molecular docking studies of 10c, 10j, and 14e in the COX-2 active site revealed similar orientation and binding interactions as selective COX-2 inhibitors with a higher liability to access the selectivity side pocket.

Synthesis, antibacterial activities and molecular docking study of thiouracil derivatives containing oxadiazole moiety

A series of novel thiouracil derivatives 9 containing an oxadiazole moiety have been synthesized by structural modification of a lead SecA inhibitor, 2. These compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus and Bacillus subtilis. Among them, compounds 9g and 9n exhibited promising antibacterial activities against the tested strains. Compound 9g was also tested for its inhibitory activities against SecA ATPase, and the IC50 value of compound 9g was 19.9 μg/mL, lower than that of compound 2 (20.8 μg/mL). Molecular docking work indicates that compound 9g likely occupies the pocket formed by SecA IRA2 and NBD domain.

Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-One Derivatives**

A series of pyrimidine-containing 4H-chromen-4-one derivatives were designed and synthesized by combining bioactive substructures. Preliminary biological activity results showed that most of the compounds displayed significant inhibitory activities in vit

Synthesis and antibacterial evaluation of thiouracil derivatives containing 1,2,4-triazolo[1,5-a]pyrimidine

A series of new thiouracil compounds containing 1,2,4-triazolo[1,5-a]pyrimidine were designed and synthesized. The in vitro antibacterial activities of the new compounds against Bacillus am-yloliquefaciens, Staphylococcus aureus and Bacillus subtilis were tested. The results showed that some of the new compounds had strong inhibitory activities against the tested bacteria. At the concentration of 50 μg/mL, the compound 12d had broad and the highest inhibitory activity with the 100% inhibition against the three tested strains, the same as norfloxacin which was used as the control.

Substituted pyrimidine-containing myricetin derivative as well as preparation method and application thereof

The invention discloses a substituted pyrimidine-containing myricetin derivative as well as a preparation method and application thereof. The general structural formula of the myricetin derivative isshown in the specification, R represents a substituted phenyl group or a substituted aromatic heterocyclic group; n is the number of carbon in a carbon chain and is 2-6; wherein the substituted phenylgroup is on the ortho-, meta-and para- position of a benzene ring and contains C1-6 alkyl groups, C1-6 alkoxyl groups, nitro groups, halogen atoms and hydrogen atoms; the aromatic heterocyclic groupis thienyl, furyl, pyrrolyl or pyridyl; and substituent groups on substituted aromatic heterocycle are ortho-, meta-and para- positions and contain C1-6 alkyl groups, C1-6 alkoxyl groups, nitro groups, halogen atoms and hydrogen atoms. The derivative can well inhibit the activity of pathogenic bacteria of plants.

Part III: Novel checkpoint kinase 2 (Chk2) inhibitors; design, synthesis and biological evaluation of pyrimidine-benzimidazole conjugates

Recently a dramatic development of the cancer drug discovery has been shown in the field of targeted cancer therapy. Checkpoint kinase 2 (Chk2) inhibitors offer a promising approach to enhance the effectiveness of cancer chemotherapy. Accordingly, in this study many pyrimidine-benzimidazole conjugates were designed and twelve feasible derivatives were selected to be synthesized to investigate their activity against Chk2 and subjected to study their antitumor activity alone and in combination with the genotoxic anticancer drugs cisplatin and doxorubicin on breast carcinoma, (ER+) cell line (MCF-7). The results indicated that the studied compounds inhibited Chk2 activity with high potency (IC50 = 5.56 nM - 46.20 nM). The studied candidates exhibited remarkable antitumor activity against MCF-7 (IG50 = 6.6 μM - 24.9 μM). Compounds 10a-c, 14 and 15 significantly potentiated the activity of the studied genotoxic drugs, whereas, compounds 9b and 20–23 antagonized their activity. Moreover, the combination of compound 10b with cisplatin revealed the best apoptotic effect as well as combination of compound 10b with doxorubicin led to complete arrest of the cell cycle at S phase where more than 40% of cells are in the S phase with no cells at G2/M. Structure-activity relationship was discussed on the basis of molecular modeling study using Molecular modeling Environment program (MOE).

Design, synthesis and antimicrobial activities of thiouracil derivatives containing triazolo-thiadiazole as SecA inhibitors

A series of novel thiouracil derivatives containing a triazolo-thiadiazole moiety (7a-7l) have been synthesized by structural modifications on a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7d and 7g were also tested for their inhibitory activities against SecA ATPase due to their promising antimicrobial activities. The inhibitory activity of compound 7d was found to be higher than that of 2. Molecular docking work suggests that compound 7d might bind at a pocket close to the ATPase ATP-binding domain.

Synthesis of 4-(thiazol-2-ylamino)-benzenesulfonamides with carbonic anhydrase I, II and IX inhibitory activity and cytotoxic effects against breast cancer cell lines

A series of 4-(thiazol-2-ylamino)-benzenesulfonamides was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory and cytotoxic activity on human breast cancer cell line MCF-7. Human (h) CA isoforms I, II and IX were included in the study. The new sulfonamides showed excellent inhibition of all three isoforms, with KIs in the range of 0.84-702 nM against hCA I, of 0.41-288 nM against hCA II and of 5.6-29.2 against the tumor-associated hCA IX, a validated anti-tumor target, with a sulfonamide (SLC-0111) in Phase I clinical trials for the treatment of hypoxic, metastatic solid tumors overexpressing CA IX. The new compounds showed micromolar inhibition of growth efficacy against breast cancer MCF-7 cell lines.

Synthesis, molecular modeling, and biological evaluation of novel benzimidazole derivatives as inhibitors of hepatitis C virus RNA replication

In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC50/90of 4d=0.123/0.321, 4f=0.145/0.345, 4h=0.129/0.432, VX-950=0.20/0.45μM, respectively) and 6d (IC50/90=0.116/0.452μM) displayed activity very similar to that of the standard. Compounds 4d, 4f, 4h, and 6d were potent HCV RNA replication inhibitors and are good drug candidates for further investigations.