955009-86-6

Upstream product

• 138386-58-0 (E)-methyl 3-[2-(triphenylphosphoranylidenamino)phenyl]-propenoate 
• 612-41-9 2-nitrocinnamic acid 
• 92-95-5 4-biphenyl isocyanate 
• 51644-96-3 5-tert-butoxycarbonylamino-1-aminopentane 
• 39228-29-0 methyl 2-nitrocinnamate 
• 462-94-2 1,5-diaminopentane 
• 92-92-2 biphenyl-4-carboxylic acid 
• 88939-75-7 methyl β-(o-aminophenyl)acrylate 
• 911840-04-5 methyl 3-[2-(3-(4-biphenyl)ureido)phenyl]acrylate 
• 839672-50-3 methyl 3-[2-((4-biphenyl)iminomethyleneamino)phenyl]acrylate 

Downstream Products

• 955011-81-1 KYS₀₅₀₈₉ 
• 1076689-75-2 2-[N-(5-aminopentyl)-N-methylamino]-3-(4-biphenylyl)-4-methoxycarbonylmethyl-3,4-dihydroquinazoline 
• 1076689-73-0 4-(N-benzylacetamino)-3-(4-biphenylyl)-2-[N-(5-aminopentyl)-N-methylamino]-3,4-dihydroquinazoline 

Relevant academic research and scientific papers

In vivo evaluation of oral anti-tumoral effect of 3,4-dihydroquinazoline derivative on solid tumor

An extension of our previously reported 3,4-dihydroquinazoline derivative is investigated. Oral anti-tumoral activity of 3,4-dihydroquinazoline derivative (KYS05090) as potent and selective T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/cnu/nu nude mice. The rate of tumor volume increment in mouse model with KYS05090-treated group was remarkably slower than that of control group. With respect to tumor weight, it exhibited 60% and 67% tumor growth inhibition through oral administration of 1 and 5 mg/kg of bodyweight, respectively, compared to control and was more potent than paclitaxel (53%). In addition, KYS05090 (10 and 50 mg/kg, po) was found to have a marked analgesic effect in acetic acid-induced writhing test, whereas it did not show any effect on hot plate test.

Anti-cancer activity of T-type calcium channel blocker in vivo

3,4-Dihydroquinazoline 1 as T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/c-nu Slc mice, which exhibited 54% tumor growth inhibition through oral administration of 8 mg/kg of body weight and was slightly less active than doxorubicin (68%). In addition, this compound was also profiled for its acute toxicity to ICR mice to afford oral LD50 value of 1,038 mg/kg of body weight.

Antitumor activity of 3,4-dihydroquinazoline dihydrochloride in A549 xenograft nude mice

In the previous article we have reported that 3,4-dihydroquinazoline 1 is a potent and selective T-type calcium channel blocker that exhibited strong anti-cancer activity in vitro. Compound 1·2HCl was further in vivo evaluated against A549 xenograft in BALB/c nude mice, which exhibited 49% tumor-weight inhibition through intravenous administration of 2 mg/kg of body weight and was more potent than doxorubicin. Moreover, compound 1·2HCl has an oral bioavailability of 98% with LD50 values of 693 mg/kg (po route) and 40.0 mg/kg (iv route) of body weight. In addition, its efficient scale-up synthetic method was developed.

3,4-DIHYDROQUINAZOLINE DERIVATIVES

The present invention relates to 3,4-dihydroquinazoline derivatives, a process of preparing them and a pharmaceutical composition including them. The 3,4-dihydroquinazoline derivatives of the present invention have excellent T-type calcium channel blocking effect and anti-cancer activity.

Synthesis and SAR study of T-type calcium channel blockers. Part II

3,4-Dihydroquinazoline derivatives have been known to be the novel and potent T-type calcium channel blockers. From a systematic variation of 3,4-dihydroquinazoline derivative 5c (KYS05043), plausible SAR results were established. It was revealed that a 5-(dimethylamino)pentylamino group at R 1, a biphenyl group at R2, and a benzyl amido group at R3 in the 3,4-dihydroquinazoline backbone are closely related with the channel selectivity (T/N-type) as well as the potency based on the discovery of 6k (KYS05090).

Discovery of potent T-type calcium channel blocker

The intensive SAR study of 3,4-dihydroquinazoline series led to the most potent compound 10 (KYS05090: IC50 = 41 ± 1 nM) against T-type calcium channel and its potency is nearly comparable to that of Kurtoxin. As a small organic molecule, this compound showed the highest blocking activity reported to date.