| RRC ID |
69538
|
| Author |
Nishimura Y, Kikuchi H, Kubo T, Arai R, Toguchi Y, Yuan B, Sunaga K, Cho H.
|
| Title |
Synthesis of 4,4-Disubstituted 3,4-Dihydropyrimidin-2(1H)-ones and -thiones, the Corresponding Products of Biginelli Reaction Using Ketone, and Their Antiproliferative Effect on HL-60 Cells.
|
| Journal |
Chem Pharm Bull (Tokyo)
|
| Abstract |
An efficient synthetic method for novel 4,4-disubstituted 3,4-dihydropyrimidin-2(1H)-ones 5 and -thiones 6 was developed. The cyclocondensation reaction of O-methylisourea hemisulfate salt 11 with 8 gives a tautomeric mixture of dihydropyrimidines 12 and 13 following acidic hydrolysis of the cyclized products to produce 5 in high yields. Thionation reaction of 5 at the 2-position smoothly proceeds to give 2-thioxo derivatives 6. These compounds 5 and 6, corresponding to the products of a Biginelli-type reaction using urea or thiourea, a ketone and a 1,3-dicarbonyl compound, have long been inaccessible and hitherto unavailable for medicinal chemistry. These methods are invaluable for the synthesis of 5 and 6, which have been inaccessible by conventional methods. Therefore, the synthetic methods established in this study will expand the molecular diversity of their related derivatives. These compounds were also assessed for their antiproliferative effect on a human promyelocytic leukemia cell line, HL-60. Treatment of 10 µM 6b and 6d showed high inhibitory activity similarly to 1 µM all-trans retinoic acid (ATRA), indicating that the 2-thioxo group and length of two alkyl substituents at the 4-position are strongly related to activity.
|
| Volume |
70(2)
|
| Pages |
111-119
|
| Published |
2022-1-1
|
| DOI |
10.1248/cpb.c21-00794
|
| PMID |
35110431
|
| MeSH |
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HL-60 Cells
Humans
Ketones / chemistry
Ketones / pharmacology*
Molecular Structure
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry
Pyrimidinones / pharmacology*
Structure-Activity Relationship
Thiones / chemical synthesis
Thiones / chemistry
Thiones / pharmacology*
|
| IF |
1.416
|
| Resource |
| Human and Animal Cells |
HL-60(RCB3683) |
