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1-Methylindazole-3-carboxylic acid

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Company Name: Capot Chemical Co.,Ltd.
Tel: +86-571-85586718
Products Intro: Product Name:Granistron hydrochloride
Purity:98%(Min,HPLC) Package:100g;1kg;5kg,10kg,25kg,50kg
Company Name: Henan DaKen Chemical CO.,LTD.
Tel: +86-371-55531817
Products Intro: Product Name:Granisetron hydrochloride
Purity:99% Package:100g,500g,1KG,10KG,100KG
Company Name: Beijing Cooperate Pharmaceutical Co.,Ltd
Tel: 010-60279497
Products Intro: Product Name:Granisetron HCl
Purity:98% Package:100G;1KG;5KG;10KG;25KG;50KG;100KG
Company Name: Henan Tianfu Chemical Co.,Ltd.
Tel: 0371-55170693
Products Intro: Product Name:107007-99-8
Purity:0.99 Package:25KG,5KG;1KG;500G
Company Name: PI & PI BIOTECH INC.
Tel: 18371201331
Products Intro: Product Name:Granisetron hydrochloride
Purity:90%+ Package:10mg, 25mg, 50mg, 100mg, Other scale please email Remarks:1-Methyl-N-[(1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide hydrochloride

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1-Methylindazole-3-carboxylic acid Basic information
Outline of Granisetron hydrochloride Domestic Market Analysis Instructions Chemical Properties Uses
Product Name:1-Methylindazole-3-carboxylic acid
Synonyms:1-methyl-n-(9-methyl-9-azabicyclo(3.3.1)non-3-yl)-1h-indazole-3-carboxamid;endo-1-methyl-n-(9-methyl-9-azabicyclo(3.3.1)non-3-yl)-1h-indazole-3-carboxa;endo-monohydrochlorid;midehydrochloride;1-METHYL-N-[(3-ENDO)-9-METHYL-9-AZABICYCLO[3.3.1]NON-3-YL]-1H-INDAZOLE-3-CARBOXAMIDE HYDROCHLORIDE;1-Methyl-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)-1H-isoindole-3-carboxamide hydrochloride;1-Methyl-N-[(1β,3α,5β)-9-methyl-9-azabicyclo[3.3.1]nonane-3-yl]-1H-indazole-3-carboxamide·hydrochloride;1-Methyl-N-[(1β,5β)-9-methyl-9-azabicyclo[3.3.1]nonane-3α-yl]-1H-indazole-3-carboxamide·hydrochloride
Product Categories:SINTROM;Other APIs;Intermediates & Fine Chemicals;Serotonin;Heterocycles;Digestive System;Pharmaceutical material and intermeidates;Active Pharmaceutical Ingredients;API;Heterocyclic Compounds;Neurochemicals;Pharmaceuticals;Granisetron;Serotonin receptor
Mol File:107007-99-8.mol
1-Methylindazole-3-carboxylic acid Structure
1-Methylindazole-3-carboxylic acid Chemical Properties
Melting point 290-292°C
storage temp. Room temp
solubility H2O: >10mg/mL
form solid
color white to off-white
Merck 14,4536
CAS DataBase Reference107007-99-8(CAS DataBase Reference)
Safety Information
Hazard Codes Xn,Xi
Risk Statements 22-62-37/38-36/37/38-36
Safety Statements 26-36-37-24/25
WGK Germany 3
RTECS NK7882200
HS Code 29399990
MSDS Information
1-Methylindazole-3-carboxylic acid Usage And Synthesis
Outline of Granisetron hydrochlorideGranisetron hydrochloride was originally developed by the British Beecham company in the mid-1980s. At 1991, the merged Smithkline-Beecham (SB) Company had pushed for the first time of 3 mg of injection Kytri1 to the market in South Africa. To date, including 1 mg of oral tablets, 1mg of injections, granisetron hydrochloride has already entered into market in United States, Britain, France, Japan, Germany, Italy and other more than forty countries and regions around the world. When the Smithkline-Beecham (SB) Company was merged with Glaxo Company, it transferred this product to the Roche Company.
Foreign research data has shown that granisetron hydrochloride has a high selectivity to receptor. Its affinity to 5-HT3 receptor is 4000 to 10000 time as high as its affinity to other receptors, such as 5-HT1, 5-HT2, dopamine D1, D1, histamine H1, benzodiazepine and opioid receptor. For comparison, the difference for ondansetron is only about 1,000 times. For the test of its prevention of cisplatin-induced emesis in ferrets, the antiemetic rates in the three dose groups of granisetron hydrochloride 2 × 0.005,2 × 0.05 and 2 × 0.5mg/kg (iv) were 93%, 96% and 100 %, respectively while for ondansetron in 2 × 2.5mg/kg, this value was 89%, demonstrating that granisetron hydrochloride exhibited a at least five times stronger efficacy of anti-emetic than ondansetron. Toxicity studies suggest that granisetron hydrochloride can achieve very excellent antiemetic effect even in small dose with only minor side effects. However, there may be sth abnormal occurring in cardiovascular system upon large doses. Since the recommended clinical dose of granisetron hydrochloride is small (3mg/d), which is only 1/25 (<1 mg/kg) of the lowest dose used in animal studies, therefore, clinical application of it is very safe. Pharmacokinetic study has shown that granisetron hydrochloride has a half-life (t1/2) of 9 h in the body of patient while this value is 4 h at healthy people, 7.7 h in elderly people and 4.9h in young people. Granisetron hydrochloride is mainly metabolized in the liver and can be excreted through the feces and urine in the form of 7-hydroxy granisetron hydrochloride and other forms of metabolic product. For patients of liver damage or liver metastases, they have reduced plasma clearance rate with the scavenging rate upon renal insufficiency being 1/4 of the normal case. It has been observed of high first pass metabolism upon oral administration with the absolute bioavailability being 60%.
Domestic Market Analysis1993, China has approved of the import of the Kytri1 injection (3 mg/ 3 mL) of British SB company, Registration No: X930279, and has allowed for in clinical trials. In 1994, the China-US Tianjin Smith Kline Pharmaceutical Co., Ltd. had used imported raw materials processing method for production of the injection of the 3mg granisetron hydrochloride and had obtained the approval of the Ministry of Health: (94) health medicine approved: J-10 number (fourth class) with the trade name being "Kay Reiter. " Currently there are a number of domestic manufacturers having their products enter into market with the number of manufacture which makes formulation being up to dozen, see Annex I for details.
China has a large population with the annual number of newly identified cancer patients being more than 1.6 million. The nausea and vomiting induced by chemotherapy and radiotherapy-induced have been one of the serious side effects that doctors and patients worry of. Therefore, new antiemetics are in urgent demand. Currently, ondansetron class of drugs has occupied most of the market antiemetic including ondansetron (ShufuLing), granisetron hydrochloride (Kytril) and tropisetron (Oubiting), wherein the ondansetron and granisetron has been accumulated of large number of clinical application experience with good response from the doctors and has played positive role on improving the domestic situation of the treatment of chemotherapy vomiting. With the localization of products, the decreasing price and the increasing income level of people, antiemetics market will be certainly greatly improved. In this case, granisetron hydrochloride, as the secondary antiemetic drug entering into market, will certainly have good market prospects.
The above information is edited by the chemicalbook of Dai Xiongfeng.
Instructions[Character]it is colorless or nearly colorless liquid clarity.
[Toxicology]This product is a highly selective 5-HT3 receptor antagonist and has excellent preventive and therapeutic effect on treating nausea and vomiting induced by radiotherapy, chemotherapy and surgery. Radiotherapy, chemotherapy and surgery and other factors can cause enterochromaffin cells to release 5-HT; 5-HT can activate the 5-HT3 receptors in central nerve or vagus nerve and cause vomiting reflex. The mechanism of this product in controlling nausea and vomiting is through antagonizing the 5-HT3 receptor in the central chemosensory area and peripheral vagus nerve terminal, further suppressing the nausea and vomiting. This product has high selectivity and no side effects such as extrapyramidal reactions, excessive sedation and so on.
[Indications]it is suitable for the treatment of nausea and vomiting induced by radiation therapy and cytotoxic drug.
[Dosage and usage amount]intravenous drip. Recommended dosage for adults is usually 3 mg. Administer it intravenously 30 minutes prior to chemotherapy. Most patients only need to be administered once with the prevention action against nausea and vomiting being more than 24 hours. The number of doses can be increased by 1-2 times if necessary, but the maximum daily dose should not exceed 9 mg and the infusion time should not be less than 5 minutes.
[Pharmacokinetics]healthy volunteers, after intravenous injection of this product for 20 or 40 μg/kg, the average peak plasma concentration was 13.7 and 42.8μg/L, the plasma elimination half-life is approximately 3.1-5.9 hours. This product is widely distributed in the body with serum protein binding rate being about 65%. Most of them are rapidly metabolized with the major metabolic pathway being N-dealkylation and conjugation after aromatic oxidation. This product is excreted through the feces and urine.
Chemical PropertiesIt is white or yellowish white crystalline powder and is odorless. It is easily soluble in water but hardly soluble in methanol, extremely hardly to be dissolved in ethanol and almost insoluble in ether. It has a melting point of 290-292 ℃. For acute toxicity LD50, female mice, male and female rats (mg/kg): 17, 25, 14, 16, respectively. Intravenous injection.
UsesIt is the selective antagonist of the 5-serotonin 3 (5-HT3) in peripheral and central nervous system.
DescriptionGranisetron hydrochloride is the second selective 5HT-3-antagonist approved for the management of nausea and vomiting induced by cancer chemotherapy.Like ondansetron, granisetron hydrochloride is superior to metoclopramide in both efficacy and side effect profile. The compound appears to be effective both as a prophylactic agent and in blocking vomiting once started.
Chemical PropertiesWhite to Off-White Crystalline Sold
OriginatorSmithKline Beecham (United Kingdom)
UsesA specific serotonin (5HT3) receptor antagonist. Used as an antiemetic. Granisetron HCl is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemothera py. Its main effect is to reduce the activity of the vagus nerve. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarini c receptor
Manufacturing ProcessA solution of 1-(phenylmethyleneamino)isatin (1.354 g, 0.0054 mol) and endo-3-amino-9-methyl-9-azabicyclo[3.3.1]nonane (0.832 g, 0.0054 mol) in dry THF (25 ml) under argon was heated to reflux for 5 hours. The solution was cooled and evaporated and the residual traces of THF were azeotropically removed with dichloromethane. The residue was triturated with ether to give the intermediate 2-(benzylidenehydrazino)-α-oxophenyl-(9-methyl-9- azabicyclo[3.3.1]non-3-yl)carboxamide as an orange powder (1.583 g, 73%).
Sodium hydride (50 mg, 60% dispersion in oil) was added to a solution of the 2-(benzylidenehydrazino)-α-oxophenyl-(9-methyl-9-azabicyclo[3.3.1]non-3-yl) carboxamide in dry THF (2.3 ml) under argon at -50°C. The resultant solution was warmed to 0°C over 20 min then cooled to -30°C and treated with methyl iodide (0.020 ml). The solution was allowed to warm to room temperature and stirred for 24 hours then filtered. The filtrate was evaporated to dryness, and triturated with chloroform to give the 2-(N-methylbenzylidenehydrazo)-α- oxophenyl-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)carboxamide as a light coloured powder (50 mg, 38%). Further trituration of the mother liquor gave a further crop, (37 mg, 28%, after recrystallisation from chloroform).
A solution of 2-(N-methylbenzylidenehydrazo)-α-oxophenyl-(9-methyl-9- azabicyclo[3.3.1]non-3-yl)carboxamide (37 mg) in methanol (1 ml) was treated with 2 N hydrochloric acid (0.1 ml) and left at room temperature for several hours. Evaporation of the solvent gave the crude product as a brown oil (36 mg). HPLC and MS analysis confirmed the structure and indicated a quantitative yield of endo-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1- methylindazole-3-carboxamide (Ganisetron).
In practice it is usually used as hydrochloride.
Brand nameKytril (Roche).
Therapeutic FunctionSerotonin antagonist
Biological Activity5-HT 3 receptor antagonist that possesses potent antiemetic activity.
Veterinary Drugs and TreatmentsGranisetron is an alternative to other 5-HT3 receptor antagonists (e.g., ondansetron or dolasetron) for the treatment of severe vomiting or prophylaxis before administering antineoplastic drugs such as cisplatin that can cause severe vomiting.
1-Methylindazole-3-carboxylic acid Preparation Products And Raw materials
Raw materialsHydrochloric acid-->Granisetron-->Iodomethane-->GRANISETRON IMPURITY B-->Sodium hydride
Tag:1-Methylindazole-3-carboxylic acid(107007-99-8) Related Product Information
Milrinone Granisetron Impurity F 1-Methyl-1H-indazole-3-carboxylic Acid Anhydride 1-Methylindazole-3-carboxylic acid N-[(1R,3r,5S)-9-azabicyclo[3.3.1]non-3-yl]-1-Methyl-1H-indazole-3-carboxaMide hydrochloride exo-Granisetron (Granisetron Impurity F) GRANISETRON-D3 Granisetron-001 7-Hydroxygranisetron Endo-3-amine-9-methyl-9-azabicyclo[3,3,1]nonane GRANISETRON IMPURITY B METSULFURON METHYL dolasetron Methyl N,N-Dimethylformamide Granisetron ALOSETRON Palonosetron Hydrochloride