4-sec-butyl-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one | 96974-48-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-sec-butyl-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one
• 英文别名: 4-sec-Butyl-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-on；3H-Pyrazol-3-one, 1,2-dihydro-1,5-dimethyl-4-(1-methylpropyl)-2-phenyl-；4-butan-2-yl-1,5-dimethyl-2-phenylpyrazol-3-one
• CAS: 96974-48-0
• 化学式: C₁₅H₂₀N₂O
• 分子量: 244.337
• InChiKey: CYGFOANTEHDZLD-UHFFFAOYSA-N

物化性质

• 熔点：
  91 °C
• 沸点：
  334.9±25.0 °C(Predicted)
• 密度：
  1.065±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-甲基-2-苯基-1,2-二氢吡唑-3-酮 、 丁酮 110.0~115.0 ℃ 、2.94 MPa 条件下， 生成 4-sec-butyl-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one
  参考文献：
  名称：

  DE962254

  摘要：

  公开号：

文献信息

• Pro-drugs of NSAIAs with very high skin and membranes penetration rates and their new medicinal uses
  申请人：Techfields Pharma Co., Ltd.

  公开号：US10233198B2

  公开（公告）日：2019-03-19

  The novel positively charged pro-drugs of NSAIAs in the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” were designed and synthesized. The compounds of the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” indicated above can be prepared from metal salts, organic base salts, or immobilized base salts of NSAIAs with suitable halide compounds. The positively charged amino groups in the pro-drugs in this invention largely increase the solubility of the drugs in water and will bond to the negative charge on the phosphate head group of membrane. Thus, the local concentration of the outside of the membrane or skin will be very high and will facilitate the passage of these pro-drugs from a region of high concentration to a region of low concentration. This bonding will disturb the membrane a little bit and may make some room for the lipophilic portion of the pro-drug. When the molecules of membrane move, the membrane may “crack” a little bit due to the bonding of the pro-drug. This will let the pro-drug insert into the membrane. At pH 7.4, only about 99% of the amino group is protonated. When the amino group is not protonated, the bonding between the amino group of the pro-drug and the phosphate head group of the membrane will disassociate, and the pro-drug will enter the membrane completely. When the amino group of the pro-drug flips to the other side of the membrane and thus becomes protonated, then the pro-drug is pulled into the cytosol, a semi-liquid concentrated aqueous solution or suspension. These pro-drugs can be used for treating and preventing diabetes (type I or/and type II), abnormal blood glucose and lipid levels, stroke, heart attack, and other heart and vascular diseases Alzheimer's diseases, Parkinson's diseases and other neurodegenerative diseases, psoriasis, discoid lupus erythematosus, systemic lupus erythematosus (SLE), autoimmune hepatitis, multiple sclerosis (MS), and other autoimmune diseases, amyotrophic lateral sclerosis (ALS), oculopharyngeal muscular dystrophy (OPMD), and other muscle disorders, inflamed hemorrhoids, cryptitis, other inflammatory conditions of the anorectum, and pruritus ani, prostatitis, prostatocystitis, varicose veins, autoimmune liver inflammation, autoimmune kidney inflammation, vein inflammation and other inflammations, skin cancers, breast cancer, colon-rectum cancer, oral cancer, and other cancers, scars, abnormal vascular skin lesions, birthmarks, moles (nevi), skin tags, aging spots (liver spots), and other skin disorders. These pro-drugs can be administered transdermally without the help of skin penetration enhancers.

  设计并合成了通式为（1、2a、2b、2c 或 2d）"结构 1、2a、2b、2c 或 2d "的新型带正电荷的非甾体抗炎药原药。上述通式（1、2a、2b、2c 或 2d）"结构 1、2a、2b、2c 或 2d "的化合物可由非甾体抗炎药物的金属盐、有机碱盐或固定碱盐与合适的卤化物化合物制备而成。本发明原药中带正电荷的氨基在很大程度上增加了药物在水中的溶解度，并会与膜上磷酸头基的负电荷结合。因此，膜或皮肤外部的局部浓度将非常高，这将有利于这些原药从高浓度区域进入低浓度区域。这种结合会稍微扰动膜，并可能为原药的亲脂部分腾出一些空间。当膜分子移动时，膜可能会因原药的粘合而 "裂开 "一点。这将使原药插入膜中。在 pH 值为 7.4 时，只有约 99% 的氨基被质子化。当氨基没有被质子化时，原药的氨基与膜的磷酸头基之间的键就会脱离，原药就会完全进入膜中。当原形药的氨基翻转到膜的另一侧并因此质子化时，原形药就会被拉入细胞质（一种半液态浓缩水溶液或悬浮液）中。这些原药可用于治疗和预防糖尿病（I 型或/和 II 型）、血糖和血脂异常、中风、心脏病发作以及其他心脏和血管疾病、牛皮癣、盘状红斑狼疮、系统性红斑狼疮（SLE）、自身免疫性肝炎、多发性硬化症（MS）和其他自身免疫性疾病、肌萎缩性脊髓侧索硬化症（ALS）、眼咽肌营养不良症（OPMD）、和其他肌肉疾病、痔疮发炎、隐窝炎、其他肛门直肠炎症和肛门瘙痒症、前列腺炎、前列腺膀胱炎、静脉曲张、自身免疫性肝脏炎症、自身免疫性肾脏炎症、静脉炎和其他炎症、皮肤癌、乳腺癌、结肠直肠癌、口腔癌和其他癌症、疤痕、异常血管性皮肤病变、胎记、痣（痦子）、皮肤标签、老年斑（肝斑）和其他皮肤疾病。这些原药无需借助皮肤渗透增强剂即可透皮给药。
• Sawa, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1937, vol. 57, p. 953,958; dtsch. Ref. S. 269
  作者：Sawa

  DOI：——

  日期：——
• PRO-DRUGS OF NSAIAS WITH VERY HIGH SKIN AND MEMBRANES PENETRATION RATES AND THEIR NEW MEDICINAL USES
  申请人：Techfields Pharma Co., Ltd.

  公开号：US20160272653A1

  公开（公告）日：2016-09-22

  The novel positively charged pro-drugs of NSAIAs in the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” were designed and synthesized. The compounds of the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” indicated above can be prepared from metal salts, organic base salts, or immobilized base salts of NSAIAs with suitable halide compounds. The positively charged amino groups in the pro-drugs in this invention largely increase the solubility of the drugs in water and will bond to the negative charge on the phosphate head group of membrane. Thus, the local concentration of the outside of the membrane or skin will be very high and will facilitate the passage of these pro-drugs from a region of high concentration to a region of low concentration. This bonding will disturb the membrane a little bit and may make some room for the lipophilic portion of the pro-drug. When the molecules of membrane move, the membrane may “crack” a little bit due to the bonding of the pro-drug. This will let the pro-drug insert into the membrane. At pH 7.4, only about 99% of the amino group is protonated. When the amino group is not protonated, the bonding between the amino group of the pro-drug and the phosphate head group of the membrane will disassociate, and the pro-drug will enter the membrane completely. When the amino group of the pro-drug flips to the other side of the membrane and thus becomes protonated, then the pro-drug is pulled into the cytosol, a semi-liquid concentrated aqueous solution or suspension. These pro-drugs can be used for treating and preventing diabetes (type I or/and type II), abnormal blood glucose and lipid levels, stroke, heart attack, and other heart and vascular diseases Alzheimer's diseases, Parkinson's diseases and other neurodegenerative diseases, psoriasis, discoid lupus erythematosus, systemic lupus erythematosus (SLE), autoimmune hepatitis, multiple sclerosis (MS), and other autoimmune diseases, amyotrophic lateral sclerosis (ALS), oculopharyngeal muscular dystrophy (OPMD), and other muscle disorders, inflamed hemorrhoids, cryptitis, other inflammatory conditions of the anorectum, and pruritus ani, prostatitis, prostatocystitis, varicose veins, autoimmune liver inflammation, autoimmune kidney inflammation, vein inflammation and other inflammations, skin cancers, breast cancer, colon-rectum cancer, oral cancer, and other cancers, scars, abnormal vascular skin lesions, birthmarks, moles (nevi), skin tags, aging spots (liver spots), and other skin disorders. These pro-drugs can be administered transdermally without the help of skin penetration enhancers.
• DE962254
  申请人：——

  公开号：——

  公开（公告）日：——