rac trans-Lafutidine

Base Information

• Chemical Name: rac trans-Lafutidine
• CAS No.: 118288-08-7
• Molecular Formula: C22H29N3O4S
• Molecular Weight: 431.556
• Hs Code.: 29349990
• European Community (EC) Number: 601-513-8
• DSSTox Substance ID: DTXSID301110782
• Nikkaji Number: J956.752F
• Wikipedia: Lafutidine
• Mol file: 118288-08-7.mol

Synonyms:rac trans-Lafutidine;206449-94-7;2-(furan-2-ylmethylsulfinyl)-N-[(E)-4-[4-(piperidin-1-ylmethyl)pyridin-2-yl]oxybut-2-enyl]acetamide;rac Lafutidine;118288-08-7;SCHEMBL3855528;DTXSID301110782;2-((Furan-2-ylMethyl)sulfinyl)-N-(4-((4-(piperidin-1-ylMethyl)pyridin-2-yl)oxy)but-2-en-1-yl)acetaMide;2-[(RS)-Furan-2-ylmethylsulfinyl]-N-{4-[4-(piperidin-1-ylmethyl) pyridin-2-yl]oxy-(2Z)-but-2-en-1-yl}acetamide;2-[(2-Furanylmethyl)sulfinyl]-N-[(2E)-4-[[4-(1-piperidinylmethyl)-2-pyridinyl]oxy]-2-buten-1-yl]acetamide;J-013489;(E)-2-(furan-2-ylmethylsulfinyl)-N-(4-(4-(piperidin-1-ylmethyl)pyridin-2-yloxy)but-2-enyl)acetamide;2-[(furan-2-yl)methanesulfinyl]-N-[(2E)-4-({4-[(piperidin-1-yl)methyl]pyridin-2-yl}oxy)but-2-en-1-yl]acetamide;2-[[(2-Furyl)methyl]sulfinyl]-N-[(E)-4-[[4-(piperidinomethyl)-2-pyridyl]oxy]-2-butenyl]acetamide

Chemical Property of rac trans-Lafutidine

Chemical Property:

• Appearance/Colour: Yellowish white crystalline powder
• Vapor Pressure: 1.12E-19mmHg at 25°C
• Melting Point: 92.7-94.9°
• Refractive Index: 1.598
• Boiling Point: 704.2 °C at 760 mmHg
• PKA: 13.13±0.46(Predicted)
• Flash Point: 379.7 °C
• PSA: 103.88000
• Density: 1.252 g/cm³
• LogP: 3.85510
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Water Solubility.: Insoluble in water
• XLogP3: 1.4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 11
• Exact Mass: 431.18787759
• Heavy Atom Count: 30
• Complexity: 569

Purity/Quality:

99% ^*data from raw suppliers

(Z)-2-((Furan-2-ylmethyl)sulfinyl)-n-(4-((3-(piperidin-1-ylmethyl)pyridin-2-yl)oxy)but-2-en-1-yl)acetamide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CCN(CC1)CC2=CC(=NC=C2)OCC=CCNC(=O)CS(=O)CC3=CC=CO3
• Isomeric SMILES: C1CCN(CC1)CC2=CC(=NC=C2)OC/C=C/CNC(=O)CS(=O)CC3=CC=CO3
• Description: Lafutidine is a second generation of H2-receptor antagonist. H2-receptor antagonist can strongly inhibit gastric acid secretion compared with conventional drugs such as antacids. Unlike conventional H2-receptor antagonist, lafutidine inhibits gastric acid secretion during daytime as well as nighttime in clinical studies in humans. Lafutidine also has gastroprotective activity independent of its acid antisecretory efficacy, preventing noxious agent-induced gastric mucosal injury and accelerating the repair process following gastric mucosal damage. It also protects experimentally induced reflux esophagitis, indomethacin-induced intestinal, and dextran sulfate sodium-induced colonic inflammation. Lafutidine is used for gastric and duodenal ulcers. It is also confirmed that lafutidine can be used as an empiric treatment and superior efficacy for primary care practice patients with dyspepsia. Lafutidine was launched in Japan for the treatment of gastritis, reflux oesophagitis and peptic ulcers. It can be prepared in eight steps from 4-(2-tetrahydropyranyloxy)-2(Z)-butenl- ol. Lafutidine is a potent and longer-acting H2 antagonist compared to other marketed compounds of its class such as cimetidine and famotidine. In contrast to other commercially available H2 antagonists, lafutidine also exerts a gastroprotective action probably via capsaicin-sensitive afferent nerves. It was clinically effective in the treatment of nonsteroidal antiinflammatory drug-induced ulcer in patients refractory to existing antiulcer agents. Lafutidine is a histamine H2 receptor antagonist with gastroprotective activity. It inhibits histamine-induced cAMP production in CHO cells expressing human histamine H2 receptors when used at a concentration of 10 nM. Intragastric administration of lafutidine (3, 10, and 30 mg/kg) reduces hemorrhagic esophageal lesion size and gastric acid secretion in a rat model of pyloric ligation-induced reflux esophagitis. It prevents 5-fluorouracil-induced intestinal mucositis, diarrhea, and body weight loss in wild-type, but not Trpv1-/- or sensory deafferented, mice when administered at doses ranging from 3 to 30 mg/kg. Lafutidine (10 mg/kg) also reduces indomethacin-induced antral ulcer size in wild-type, but not chemically-deafferented, rats.
• Uses: (Z)-2-((Furan-2-ylmethyl)sulfinyl)-n-(4-((3-(piperidin-1-ylmethyl)pyridin-2-yl)oxy)but-2-en-1-yl)acetamide is a Histaminic H2 receptor antagonists in ulcer disease. Also, it is a model compound used to investigate the binding mechanism between antiulcer drugs and human serum albumin (HSA). Second generation histamine H2-receptor antagonist. Antiulcerative Lafutidine, a newly developed histamine H(2)-receptor antagonist, inhibits gastric acid secretion

Technology Process of rac trans-Lafutidine

There total 13 articles about rac trans-Lafutidine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 94.6%

(2Z)-4-({4-[(piperidin-1-yl)methyl]pyridin-2-yl}oxy)but-2-en-1-amine + p-nitrophenyl 2-(furfurylsulfinyl)acetate (123855-55-0) → lafutidine (118288-08-7,206449-93-6,206449-94-7)

Guidance literature:

In dichloromethane; at 25 - 30 ℃;

Reference yield:

2-Bromo-4-[1,3]dioxolan-2-yl-pyridine (118289-18-2) → lafutidine (118288-08-7,206449-93-6,206449-94-7)

Guidance literature:

Multi-step reaction with 8 steps

1: 87 percent / NaOH, K₂CO₃, n-Bu₄NHSO₄ / toluene / 18 h / Ambient temperature

2: 90 percent / pyridinium p-toluenesulfonate, ethanol / 18 h / 55 °C

3: SOCl₂, Et₃N / CH₂Cl₂ / 1 h / 0 °C

4: n-Bu₄NHSO₄ / acetonitrile / 18 h / Heating

5: 78 percent / NH₂NH₂*H₂O / methanol / 10 h / Heating

6: 91 percent / tetrahydrofuran / 18 h / Ambient temperature

7: 52 percent / p-TsOH, H₂O / acetone / 18 h / Heating

8: 2.) NaBH₄ / 1.) EtOH, 3 h, 2.) EtOH, 16 h

With sodium hydroxide; sodium tetrahydroborate; thionyl chloride; ethanol; water; tetra(n-butyl)ammonium hydrogensulfate; pyridinium p-toluenesulfonate; potassium carbonate; toluene-4-sulfonic acid; hydrazine hydrate; triethylamine; In tetrahydrofuran; methanol; dichloromethane; acetone; toluene; acetonitrile;

DOI:10.1248/cpb.46.616

Reference yield:

(Z)-4-(4-[1,3]Dioxolan-2-yl-pyridin-2-yloxy)-but-2-enylamine (118289-22-8) → lafutidine (118288-08-7,206449-93-6,206449-94-7)

Guidance literature:

Multi-step reaction with 3 steps

1: 91 percent / tetrahydrofuran / 18 h / Ambient temperature

2: 52 percent / p-TsOH, H₂O / acetone / 18 h / Heating

3: 2.) NaBH₄ / 1.) EtOH, 3 h, 2.) EtOH, 16 h

With sodium tetrahydroborate; water; toluene-4-sulfonic acid; In tetrahydrofuran; acetone;

DOI:10.1248/cpb.46.616

upstream raw materials:

piperidine

N-[(Z)-4-(4-Formyl-pyridin-2-yloxy)-but-2-enyl]-2-(furan-2-ylmethanesulfinyl)-acetamide

2-Bromo-4-[1,3]dioxolan-2-yl-pyridine

(Z)-4-(4-[1,3]Dioxolan-2-yl-pyridin-2-yloxy)-but-2-enylamine

Refernces

• 1、 Hirakawa, Nobuhiko,Matsumoto, Hajime,Hosoda, Akihiko,Sekine, Akihiro,Yamaura, Tetsuaki,Sekine, Yasuo. "A novel histamine 2(H2) receptor antagonist with gastroprotective activity. II. Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2-furfurylsulfinyl acetamide derivatives with heteroaromatic rings". . p. 616 - 622. Retrieved 1998.
• 2、 -. "Preparation method and application of lafutidine and intermediate thereof". Paragraph 0107-0108; 0111-0115; 0118-0122; 0125-0129; 0132. . Retrieved 2020/01/12.