6-phenyl-4-pyridazinecarboxylic acid | 1425498-70-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-phenyl-4-pyridazinecarboxylic acid
• 英文别名: 6-Phenylpyridazine-4-carboxylic acid；6-phenylpyridazine-4-carboxylic acid
• CAS: 1425498-70-9
• 化学式: C₁₁H₈N₂O₂
• mdl: MFCD22398932
• 分子量: 200.197
• InChiKey: SNUNRNLGUCRYRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Dab(Boc)-Thr(tBu)-Dab(Boc)-cyclo[Dab-Dab(Boc)-DPhe-Leu-Dab(Boc)-Dab(Boc)-Thr(tBu)] 、 6-phenyl-4-pyridazinecarboxylic acid 在 N-甲基吗啉 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Discovery of Dap-3 Polymyxin Analogues for the Treatment of Multidrug-Resistant Gram-Negative Nosocomial Infections

  摘要：

  We report novel polymyxin analogues with improved antibacterial in vitro potency against polymprin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.

  DOI：

  10.1021/jm400416u

文献信息

• [EN] 2,3-DIHYDRO-4H-BENZO[B][1,4]OXAZIN-4-YL)(5-(PHENYL)-PYRIDIN-3-YL)METHANONE DERIVATIVES AND SIMILAR COMPOUNDS AS CYP11A1 INHIBITORS FOR THE TREATMENT OF PROSTATE CANCER<br/>[FR] DÉRIVÉS DE 2,3-DIHYDRO-4H-BENZO[B][1,4]OXAZIN-4-YL)(5-(PHÉNYL)-PYRIDIN-3-YL)MÉTHANONE ET COMPOSÉS SIMILAIRES SERVANT D'INHIBITEURS DE CYP11A1 POUR LE TRAITEMENT DU CANCER DE LA PROSTATE
  申请人：ORION CORP

  公开号：WO2022117920A1

  公开（公告）日：2022-06-09

  The present invention relates to compounds of formula (I) wherein A is a 3-10 membered carbocyclyl or a 4-12 membered heterocyclyl containing 1-4 heteroatoms selected from O, N or S; B is any of the following groups (1) (2) or (3 ); C is any of the following groups (1') (2') (3") or (4') G1is CH2, NH or O; G2and G3are, independently, is CH or N: Z is -C(O)-, -SO2-, -C1-3alkyl- or -CH2-C(O)-; L is a bond, -C1-7alkyl- or -C1-7alkenyl-; The compounds of formula (I) are cytochrome P450 monooxygenase 11A1 (CYP11A1) inhibitors. The compounds are useful as medicaments in the treatment of steroid receptor, for example androgen receptor or estrogen receptor, dependent diseases and conditions, such as cancer including prostate cancer and estrogen cancer.

  本发明涉及式(I)化合物，其中A是3-10个成员的碳环或4-12个成员的杂环，其中包含1-4个从O、N或S中选择的杂原子；B是以下任意一组(1)、(2)或(3)；C是以下任意一组(1')、(2')、(3")或(4')；G1是CH2、NH或O；G2和G3分别是CH或N；Z是-C(O)-、-SO2-、-C1-3烷基-或- -C(O)-；L是键、-C1-7烷基-或-C1-7烯基-；式(I)化合物是细胞色素P450单加氧酶11A1(CYP11A1)抑制剂。这些化合物在治疗类固醇受体，例如雄激素受体或雌激素受体依赖性疾病和病况，如包括前列腺癌和雌激素癌在内的癌症中，作为药物是有用的。