4-methyl-2-((trimethylsilyl)ethynyl)thiazole | 1365214-91-0

• 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-methyl-2-((trimethylsilyl)ethynyl)thiazole
• 英文别名: trimethyl-[2-(4-methylthiazol-2-yl)ethynyl]silane；4-Methyl-2-((trimethylsilyl)ethynyl)thiazole；trimethyl-[2-(4-methyl-1,3-thiazol-2-yl)ethynyl]silane
• CAS: 1365214-91-0
• 化学式: C₉H₁₃NSSi
• 分子量: 195.36
• InChiKey: DJVMNCQGQCKMAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-methyl-2-((trimethylsilyl)ethynyl)thiazole 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 ammonium acetate 、 potassium carbonate 、 二甲基亚砜 、 三乙胺 、 palladium dichloride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 55.25h， 生成 2-{[5-(4-hydroxyphenyl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Design, synthesis, and evaluation of novel 4-thiazolylimidazoles as inhibitors of transforming growth factor-β type I receptor kinase

  摘要：

  A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-beta-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-{[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1, 3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50 = 8.2 nM) as well as inhibitory activity against TGF-beta-induced Smad2/3 phosphorylation at a cellular level (IC50 = 32 nM). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.066
• 作为产物：
  描述：

  2-碘-4-甲基噻唑 、 三甲基乙炔基硅 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 反应 19.0h， 以62%的产率得到4-methyl-2-((trimethylsilyl)ethynyl)thiazole
  参考文献：
  名称：

  Design, synthesis, and evaluation of novel 4-thiazolylimidazoles as inhibitors of transforming growth factor-β type I receptor kinase

  摘要：

  A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-beta-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-{[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1, 3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50 = 8.2 nM) as well as inhibitory activity against TGF-beta-induced Smad2/3 phosphorylation at a cellular level (IC50 = 32 nM). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.066

文献信息

• [EN] NOVEL GALACTOSIDE INHIBITOR OF GALECTINS<br/>[FR] NOUVEAU GALACTOSIDE COMME INHIBITEUR DE GALECTINES
  申请人：GALECTO BIOTECH AB

  公开号：WO2021001528A1

  公开（公告）日：2021-01-07

  The present invention relates to a D-galactopyranose compound of formula (1) wherein the pyranose ring is α-D-galactopyranose, and these compounds are high affinity galectin-1 and/or galectin 3 inhibitors for use in treatment of inflammation; fibrosis; scarring; keloid formation; aberrant scar formation; surgical adhesions; septic shock; cancer; metastasising cancers; autoimmune diseases, metabolic disorders; heart disease; heart failure; pathological angiogenesis; eye diseases; atherosclerosis; metabolic diseases; diabetes type I; diabetes type II; insulin resistance; Diastolic heart failure; asthma; liver disorders.

  本发明涉及一种式（1）的D-半乳糖吡喃糖类化合物，其中吡喃糖环为α-D-半乳糖吡喃糖，这些化合物是高亲和力的galectin-1和/或galectin 3抑制剂，用于治疗炎症；纤维化；瘢痕形成；瘢痕增生；异常瘢痕形成；手术粘连；脓毒性休克；癌症；转移性癌症；自身免疫疾病；代谢紊乱；心脏病；心力衰竭；病理性血管生成；眼部疾病；动脉粥样硬化；代谢性疾病；糖尿病I型；糖尿病II型；胰岛素抵抗；舒张期心力衰竭；哮喘；肝脏疾病。
• [EN] NOVEL GALACTOSIDE INHIBITOR OF GALECTINS<br/>[FR] NOUVEL INHIBITEUR GALACTOSIDE DE GALECTINES
  申请人：GALECTO BIOTECH AB

  公开号：WO2021004940A1

  公开（公告）日：2021-01-14

  The present invention relates to a D-galactopyranose compound of formula (1) wherein the pyranose ring is beta-D-galactopyranose, and these compounds are high affinity galectin-1 and/or 3 inhibitors for use in treatment of inflammation; Inflammation induced thrombosis; Atopic dermatitis; Acute coronary syndrome; fibrosis, such as pulmonary fibrosis, liver fibrosis, kidney fibrosis, ophthalmological fibrosis and fibrosis of the skin and heart; local fibrosis such as Dupuytren's disease and Peyronie's disease; fibrotic complications of other therapies such as coronary stents, bile duct stents, cerebral artery stents, ureter stents; scleroderma; scarring; keloid formation; covid-19; acute lung injury; ARDS; viral pneumonitis, aberrant scar formation; surgical adhesions; septic shock; cancer, such as colorectal cancer, other gastrointestinal carcinomas such as pancreatic cancer, gastric cancer, biliary tract cancer, lung cancers, mesothelioma, female cancers like breast cancer, ovarian cancer, uterine cancer, cancer of the cervix uteri, cancer of the salpingx, cerebral cancers such as medulloblastomao, glioma, meningioma, sarcomas of the bones and muscles and other sarcomas, leukemias and lymphomas, such as T-cell lymphomas; transplant rejection; metastasising cancers; ageing; Dementia; Alzheimers; TGFbeta driven bone disease such as osteogenesis imperfecta; Pulmonary hypertension; autoimmune diseases, such as psoriasis, rheumatoid arthritis, Rheumatoid lung; Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; viral infections such as influenza virus, HIV, Herpes virus, Coronaviruses, Hepatitis C; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or a disease or condition associated with ocular angiogenesis, e.g. neovascularization related to cancer; and eye diseases, such as age-related macular degeneration and corneal neovascularization; atherosclerosis; metabolic diseases; diabetes; type I diabetes; type 2 diabetes; insulin resistens; obesity; Marfans syndrome; Loeys–Dietz syndrome; nephropathy; Diastolic HF; fibrotic lung complications of aPD1 and other CPI therapies; asthma and other interstitial lung diseases, including Hermansky-Pudlak syndrome, liver disorders, such as non- alcoholic steatohepatitis or non-alcoholic fatty liver disease; uterine disease such as uterine fibroids and uterine or cervical fibrosis.

  本发明涉及一种化学式（1）中的D-半乳糖吡喃糖类化合物，其中吡喃糖环为β-D-半乳糖吡喃糖，并且这些化合物是高亲和力的galectin-1和/或3抑制剂，用于治疗炎症；炎症诱导性血栓形成；特应性皮炎；急性冠状动脉综合征；纤维化，如肺纤维化、肝纤维化、肾脏纤维化、眼科纤维化和皮肤和心脏的纤维化；局部纤维化，如杜普伊特伦氏病和佩龙氏病；其他治疗的纤维化并发症，如冠状支架、胆管支架、脑动脉支架、输尿管支架；硬皮病；瘢痕形成；瘢痕增生；新冠肺炎；急性肺损伤；ARDS；病毒性肺炎；异常瘢痕形成；手术粘连；脓毒性休克；癌症，如结直肠癌、其他胃肠癌，如胰腺癌、胃癌、胆道癌、肺癌、间皮瘤、女性癌症如乳腺癌、卵巢癌、子宫癌、宫颈癌、输卵管癌、脑癌如髓母细胞瘤、胶质瘤、脑膜瘤、骨骼和肌肉的肉瘤和其他肉瘤、白血病和淋巴瘤，如T细胞淋巴瘤；移植排斥；转移性癌症；衰老；痴呆症；阿尔茨海默病；TGFbeta驱动的骨疾病，如骨发育不全；肺动脉高压；自身免疫疾病，如牛皮癣、类风湿关节炎、类风湿肺；克罗恩病、溃疡性结肠炎、强直性脊柱炎、系统性红斑狼疮；病毒感染，如流感病毒、HIV、疱疹病毒、冠状病毒、丙型肝炎；代谢紊乱；心脏病；心力衰竭；病理性血管生成，如眼部血管生成或与眼部血管生成相关的疾病或症状，例如与癌症相关的新血管生成；眼部疾病，如老年性黄斑变性和角膜新血管生成；动脉粥样硬化；代谢性疾病；糖尿病；1型糖尿病；2型糖尿病；胰岛素抵抗；肥胖；马凡氏综合征；洛伊斯-迪茨综合征；肾病；舒张期心力衰竭；aPD1和其他CPI疗法的肺纤维化并发症；哮喘和其他间质性肺疾病，包括赫尔曼斯基-普德拉克综合征、肝脏疾病，如非酒精性脂肪性肝炎或非酒精性脂肪肝病；子宫疾病，如子宫肌瘤和子宫或宫颈纤维化。
• [EN] NOVEL GALACTOSIDE INHIBITOR OF GALECTINS<br/>[FR] NOUVEAU GALACTOSIDE INHIBITEUR DE GALECTINES
  申请人：GALECTO BIOTECH AB

  公开号：WO2022136365A1

  公开（公告）日：2022-06-30

  The present invention relates to a D-galactopyranose compound of formula (1) wherein the pyranose ring is β-D-galactopyranose. A1 is (II) wherein the asterix * indicates the nitrogen atom of the triazole ring that is covalently attached to the galactopyranose; these compounds are high affinity galectin-1 and/or 3 inhibitors for use in treatment of inflammation.

  本发明涉及一种公式（1）的D-半乳糖吡喃糖化合物，其中吡喃环为β-D-半乳糖吡喃糖。A1为（II），其中星号*表示三唑环的氮原子与半乳糖共价连接;这些化合物是高亲和力的galectin-1和/或3抑制剂，用于治疗炎症。
• Design, synthesis, and evaluation of novel 4-thiazolylimidazoles as inhibitors of transforming growth factor-β type I receptor kinase
  作者：Hideaki Amada、Yoshinori Sekiguchi、Naoya Ono、Yuko Matsunaga、Takeshi Koami、Hajime Asanuma、Fumiyasu Shiozawa、Mayumi Endo、Akiko Ikeda、Mari Aoki、Natsuko Fujimoto、Reiko Wada、Masakazu Sato

  DOI：10.1016/j.bmcl.2012.01.066

  日期：2012.3

  A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-beta-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1, 3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50 = 8.2 nM) as well as inhibitory activity against TGF-beta-induced Smad2/3 phosphorylation at a cellular level (IC50 = 32 nM). (C) 2012 Elsevier Ltd. All rights reserved.