Yellowish-brown plates or needles or yellow solid. (NTP, 1992)
颜色/状态：
YELLOW NEEDLES OR PLATES FROM ACETONE
稳定性/保质期：
稳定，易吸湿，光敏性。避免与强氧化剂接触。
计算性质
辛醇/水分配系数(LogP)：
1.1
重原子数：
14
可旋转键数：
0
环数：
2.0
sp3杂化的碳原子比例：
0.0
拓扑面积：
71.3
氢给体数：
0
氢受体数：
3
ADMET
代谢
在大鼠中产生4-羟基氨基喹啉-N-氧化物；SUGIMURA, T, OKABE, K, & NAGAO, M, 癌症研究, 26, 1717 (1966)；在小鼠中；KAWAZOE, Y, UEHARA, N, ARAKI, M, & TAMURA, M, GANN, 60, 617 (1969)。/来自表格/
YIELDS 4-HYDROXYLAMINOQUINOLINE-N-OXIDE IN RATS; SUGIMURA, T, OKABE, K, & NAGAO, M, CANCER RES, 26. 1717 (1966); IN MICE; KAWAZOE, Y, UEHARA, N, ARAKI, M, & TAMURA, M, GANN, 60, 617 (1969). /FROM TABLE/
... IS RAPIDLY REDUCED BY RAT-LIVER SOL FRACTION. ... RATE OF REDN IN VITRO OF SERIES OF NITROQUINOLINE N-OXIDES CORRELATES WITH THEIR CARCINOGENICITY. SOL ENZYME RESPONSIBLE FOR THIS REDN IS THOUGHT TO BE DT DIAPHORASE, ENZYME (FLAVOPROTEIN) WHICH CATALYZES OXIDN OF NADPH & NADH.
EFFECTS WERE STUDIED OF SODIUM CHLORIDE ON PRODUCTION OF GASTRIC CARCINOMAS BY 4-NITROQUINOLINE-1-OXIDE IN MALE WISTAR RATS. NACL GIVEN ALONE HAD NO APPARENT CARCINOGENICITY BUT WHEN ADMIN WITH 4-NITROQUINOLINE-1-OXIDE IT ENHANCED CARCINOGENIC EFFECTS IN STOMACH.
ADMIN OF 4-NITROQUINOLINE 1-OXIDE TO RATS FOLLOWING PRIOR TREATMENT WITH N-METHYL-N'-NITRO-N-NITROSOGUANIDINE RESULTED IN UNDIFFERENTIATED ADENOCARCINOMAS IN 29% OF TUMORS INDUCED IN GLANDULAR STOMACH.
The modifying effect of three doses of DL-alpha-difluoromethylornithine given orally during the post-initiation phase of tongue carcinogenesis initiated by 4-nitroquinoline 1-oxide was studied in male ACI/N rats. Animals were given 4-nitroquinoline 1-oxide at 20 ppm for 8 wk in the drinking water to induce tongue neoplasms. One wk after the stop of 4-nitroquinoline 1-oxide treatment, rats were transferred to the drinking water containing DL-alpha-difluoromethylornithine at concn of 100, 1000, and 2000 ppm for 25 wk. The other groups consisted of rats given 2000 ppm DL-alpha-difluoromethylornithine alone or untreated rats. Thirty four wk after the start of the experiment, all animals were necropsied, and the incidences of neoplasms and preneoplastic lesions in the tongue, polyamine levels in the bloods and tongue tissues, and cell proliferation estimated by the number and area of silver stained nucleolar organizer regions in the tongue epithelium were compared among the groups. Feeding of DL-alpha-difluoromethylornithine at all doses significantly inhibited the incidence of tongue neoplasms compared to the group given 4-nitroquinoline 1-oxide alone. DL-alpha-difluoromethylornithine at levels of 1000 and 2000 ppm significantly reduced the incidence of preneoplastic lesions of the tongue. Results analyzed by the linear regression method suggested a dose dependent inhibition in the incidences of neoplastic and preneoplastic lesions of the tongue with increasing levels of DL-alpha-difluoromethylornithine. Increased levels in polyamines in the blood and tongue tissue were significantly suppressed by the treatment of DL-alpha-difluoromethylornithine. Also, silver stained nucleolar organizer region indices were significantly reduced by the DL-alpha-difluoromethylornithine exposure. These results indicate that increasing levels of DL-alpha-difluoromethylornithine in the drinking water inhibited 4-nitroquinoline 1-oxide induced tongue carcinogenesis in a dose dependent manner and such inhibition was related to reduction in the polyamine levels of blood and tissue and decrease in the cell proliferation.
The modifying effects of indole-3-carbinol and sinigrin on the initiation and post-initiation phases of tongue carcinogenesis induced by 4-nitroquinoline 1-oxide were investigated in male ACI/N rats. Rats were divided into eight groups: group 1 was given 4-nitroquinoline 1-oxide (10 ppm) in the drinking water for 12 wk, starting at 7 wk of age; groups 2 and 3 were given 4-nitroquinoline 1-oxide and fed the diets containing indole-3-carbinol (1,000 ppm) and sinigrin (1,200 ppm) for 14 wk, respectively, starting at 6 wk of age; groups 4 and 5 were given 4-nitroquinolin 1-oxide and then they were fed indole-3-carbinol and sinigrin containing diets for 23 wk, respectively, starting one wk after 4-nitroquinoline 1-oxide exposure; groups 6 and 7 were given indole-3-carbinol and sinigrin alone, respectively, during the experiment; group 8 served as an untreated control. At the termination of the experiment (wk 37), the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) in group 2 (1/15, 7%), group 3 (1/15, 7%), group 4 (3/15, 20%) or group 5 (2/15, 13%) was significantly smaller than that in group 1 (12/17, 71%) (p= 0.0003, p= 0.005 or p= 0.002). No tongue carcinomas developed in rats of groups 2, 3, and 5. Similarly, the incidence of preneoplastic lesions (hyperplasia and dysplasia) of the tongue in group 2 (11/15, 73%), group 3 (10/15, 67%), group 4 (11/15, 73%) or group 5 (10/15, 67%) was significantly lower than tha in group 1 (17/17, 100%) (p= 0.04 or p= 0.02). There were no tongue neoplasms in rats of groups 6, 7, and 8. Administration of indole-3-carbinol and sinigrin also caused significant decreases in the number and area of silver stained nucleolar organizer regions protein, a new cell proliferation index, of tongue squamous epithelium. Thus, indole-3-carbinol and sinigrin inhibited rat tongue carcinogenesis in both the initiation and post-initiation phases, when administered in these respective phases together with, or following treatment with, 4-nitroquinoline 1-oxide.
Normal human fibroblasts (the OUMS-24 strain), derived from a 6 wk old human embryo, were transformed (into the OUMS-24F line) and immortalized by repeated treatments (59 times) with 4-nitroquinoline 1-oxide. Treatment began during primary culture and ended at the 51st population doubling level. At the 57th population doubling level (146 days after the last treatment), morphologically altered, epithelial type cells appeared, began to grow and became immortal (now past the 100th population doubling level). However, the control fibroblasts, which were not treated with 4-nitroquinoline 1-oxide, senesced at the 62nd population doubling level. The finding that extensive, repeated treatments with 4-nitroquinoline 1-oxide are required for the immortalization of normal human cells, indicates that multiple mutational events are involved in the immortalization of human cells in general. In other words, immortalization itself seems to be a multi-step process. Karyotypic analysis showed that many cells were hypodiploid before immortalization, but that afterwards chromosomes were distributed broadly in the diploid to tetraploid regions. The immortalized cells showed amplification and enhanced expression of c-myc. Two-dimensional electrophoretic analysis showed that the number of disappearing cellular proteins was greater than the number of the newly appearing ones after the cells became immortalized.
[EN] PYRIMIDINE INDOLE DERIVATIVES FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE PYRIMIDINE ET D'INDOLE POUR LE TRAITEMENT DU CANCER
申请人：ASTRAZENECA AB
公开号：WO2010073034A1
公开（公告）日：2010-07-01
There is provided pyrimidinyl indole compounds of Formula (I), or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly for treating cancer.
Studies on tertiary amine oxides. LXXIII. Substitution of aromatic N-oxides with radicals produced from azo compounds.
作者：TOSHIYASU ENDO、SEITARO SAEKI、MASATOMO HAMANA
DOI：10.1248/cpb.29.3105
日期：——
Treatment of quinoline 1-oxide (1a) with α, α'-azobisisobutyronitrile (AIBN) ordimethyl α, α'-azobisisobutyrate in boiling benzene for 5 h affords 2-(1-cyano-1-methylethyl) quinoline (2a) or 2-(1-methoxycarbonyl-1-methylethyl) quinoline (4) in 31.9 or 24.9% yield, respectively, accompanied with a small amount of quinoline in each case. The 1-oxides of lepidine, 3, 2'-diquinolyl and 4-nitroquinoline (1c, 1d and 1e), and isoquinoline 2-oxide (6) similarly react with AIBN to produce the corresponding α-substituted products (2c, 2d, 2e and 7). The reaction of pyridine 1-oxide (8) gives not only the 2-substituted pyridine (9 : 1.5%) but also the 4-substituted one (10 : 3.0%). On the other hand, the reactions of 1a and 6 with phenylazotriphenylmethane in boiling benzene afford the α-phenyl N-oxides (12 : 17.2% and 14 : 34.5%) and their deoxygenated products (13 : 3.5% and 15 : 2.9%).
Hypervalent Iodine(III)‐Mediated Regioselective Cyanation of Quinoline
<i>N</i>
‐Oxides with Trimethylsilyl Cyanide
作者：Feng Xu、Yuqin Li、Xin Huang、Xinjie Fang、Zhuofei Li、Hongshuo Jiang、Jingyi Qiao、Wenyi Chu、Zhizhong Sun
DOI：10.1002/adsc.201801185
日期：2019.2
A regioselective cyanation of quinoline N‐oxides with trimethylsilyl cyanide was developed by using (Diacetoxyiodo) benzene (PIDA) as mediated hypervalentiodine(III) reagent under metal‐free and base‐free reaction conditions to obtain 2‐cyanoquinolines. The efficient PIDA reagent could play the role of an activator of the substrates and an accelerator of N−O bond cleavage. The reaction system featured
Catalyst-free synthesis of substituted pyridin-2-yl, quinolin-2-yl, and isoquinolin-1-yl carbamates from the corresponding hetaryl ureas and alcohols
作者：Svetlana O. Kasatkina、Kirill K. Geyl、Sergey V. Baykov、Irina A. Boyarskaya、Vadim P. Boyarskiy
DOI：10.1039/d1ob00783a
日期：——
catalyst-free synthesis of N-pyridin-2-yl, N-quinolin-2-yl, and N-isoquinolin-1-yl carbamates utilizes easily accessible N-hetaryl ureas and alcohols. The proposed environmentally friendly technique is suitable for the good-to-high yielding synthesis of a wide range of N-pyridin-2-yl or N-quinolin-2-yl substituted carbamates featuring electron-donating and electron-withdrawing groups in the azine rings
N-吡啶-2-基、N-喹啉-2-基和N-异喹啉-1-基氨基甲酸酯的新型无催化剂合成利用容易获得的N-杂芳基脲和醇。所提出的环保技术适用于从良好到高产率合成各种N-吡啶-2-基或N-quinolin-2-yl 取代的氨基甲酸酯，其在吖嗪环中具有给电子和吸电子基团，并且在氧原子处含有各种伯、仲甚至叔烷基取代基（48-94%；31 个例子）。DFT计算和实验研究表明，反应是通过异氰酸异氰酸杂酯中间体的形成进行的。该方法可用于获得N-异喹啉-1-基氨基甲酸酯，但收率较低，苯并[ h ]喹啉-2-基氨基甲酸乙酯也已成功合成（68%）。
Pyridine and related aza heterocycle derivatives as cardiovascular agents
申请人：AMERICAN CYANAMID COMPANY
公开号：EP0446604A3
公开（公告）日：1992-02-19
Novel pharmaceutical compounds and compositions having nitrogen containing ring systems which may be represented by the following structural formula:
wherein R₁ or R₃ is a moiety of the formula:
wherein R₆ is selected from either hydrogen or acetyl; R₇ is selected from 2, 3 or 4-pyridyl or 1-imidazolyl and Q is -(CH₂)n, where n is an integer from 1 to 5 and R₁ and R₂, R₂ and R₃, R₃ and R₄ or R₄ and R₅ taken together may be -CH=CH-CH=CH-. The compounds and compositions are useful as inhibitors of thromboxane synthetase and in the treatment of hypertension and arrythmia in mammals.
