• 대한화학회지
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• 제51권3호
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• pp.244-250
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• 2007

항암작용이 기대되는 일련의 새로운 6-allylthio-3-aminopyridazine 유도체를 allylthiolation, amination을 이용하여 합성하였다. 피리다진 핵은 hydrazine monohydrate와 maleic anhydride의 축합반응으로 제조하였다. 3,6- Dichloropyridazine은 3,6-dihydroxypyridazine을 POCl3에 가하여 합성하였다. 6-Allythio-3-chloropyridazine은 3,6- dichloropyridazine에 allylmercaptan과 sodium hydroxide을 이용하여 얻었다. Morpholine, piperazine, pyrazole, imidazole, pyrrolidine, piperidine, perhydroazepine 및 perhydroazocine와 같은 질소 친핵체를 갖는 hetero환을 피리 다진 환의 3번 위치에 도입시켜 6-allylthio-3-aminopyridazine 합성하였다. 이 과정은 아민 친핵체의 친핵성 치환반응 으로 n-buthanol에서 NH4Cl를 가하고 24~48시간 동안 환류시켜 진행하였다.

• 약학회지
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• 제49권1호
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• pp.56-59
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• 2005

We synthesized new N-substituted 3-amino-6-chloropyridazine derivatives which were expected to retain biological activity. All synthetic process from pyridazine to 3-aminopyridazines could be carried out conveniently in high yield. N-Substituted 3-amino-6-chloropyridazine derivatives were prepared through amination and acylation from 3,6-dichloropyridazine. 3-Amino-6-chloropyridazine was prepared from the reaction of 3,6-dichloropyridazine with liquid ammonia under autoclave for 6 hrs. The refluxing of 3-amino-6-chloropyridazine and the corresponding acid anhydride for $1{\sim}2$ hrs afforded the N-substituted 3-amino-6-chloropyridazines. Alkyl chain of N-substituent was prolonged to six carbon (hexanoic acid).

• 약학회지
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• 제60권3호
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• pp.101-106
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• 2016

Allylthiopyridazine derivatives were synthesized and evaluated for anti-proliferative activities in the previous study. In this study, selected two allylthiopyridazine derivatives (compound I, 3-heptylamino-6-allylthiopyridazine and compound II, 3-dipentylamino-6-allylthiopyridazine) were assessed for cytotoxicity and chronic proliferation in human colon carcinoma RKO cells. Two derivatives dose-dependently inhibited cell viability and proliferation. To elucidate the anticancer mechanism of two derivatives, we investigated the expression level of apoptosis-related proteins in RKO cells. Compound I induced the activation of JNK and expression of p53 and p21. On the other hand, compound II showed no change of p53 level. Interestingly, compound II inhibited the nuclear translocation of NF-${\kappa}B$. This result suggested that compound II suppressed cell proliferation. These different mechanisms of these compounds might have occurred through different steric conformation.

• 대한화학회지
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• 제47권6호
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• pp.591-596
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• 2003

아미노싸이에노피리다진(1a, b)과 아미노싸이에노쿠마린(2)은 DMFDMA와 축합반응을 하여 아미딘(3a, b)을 형성한다. 이 화합물들을 N-페닐말레이마이드와 반응시키면 화합물 9와 10이 얻어진다. 반면에 3a, b, 4, 18, 19, 20을 말레산 무수물과 반응시키면 포밀 유도체인 5a, b, 6, 21, 22, 23 들이 얻어진다. 아미딘 화합물 3a, b 를 다이에틸 퓨마레이트와 반응시키면 가수분해산물인 아미딘 14를 거쳐 11이 얻어진다. N-페닐말레이마이드를 마이크로웨이브 오븐에서 반응시키면 [2+2]와 [2+2+2] 고리첨가반응 산물이 얻어진다.