886362-07-8

Basic information

• Product Name: 4-METHOXY-1H-INDAZOL-3-AMINE
• Synonyms: 4-METHOXY-1H-INDAZOL-3-AMINE;1H-Indazol-3-aMine, 4-Methoxy-;4-(Methyloxy)-1H-indazol-3-amine;4-Methoxy-1H-indazol-3-ylamine
• CAS NO: 886362-07-8
• Molecular Formula: C₈H₉N₃O
• Molecular Weight: 163.18
• EINECS: 200-528-9
• Product Categories: Amines;Building Blocks;C8;Chemical Synthesis;Ethers;Nitrogen Compounds;Organic Building Blocks;Oxygen Compounds
• Mol File: 886362-07-8.mol

Chemical Properties

• Melting Point: 85-87°C
• Boiling Point: 406.3 °C at 760 mmHg
• Flash Point: 199.5 °C
• Appearance: /
• Density: 1.344
• Vapor Pressure: 8.21E-07mmHg at 25°C
• Refractive Index: 1.712
• PKA: 15.19±0.40(Predicted)
• CAS DataBase Reference: 4-METHOXY-1H-INDAZOL-3-AMINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-METHOXY-1H-INDAZOL-3-AMINE(886362-07-8)
• EPA Substance Registry System: 4-METHOXY-1H-INDAZOL-3-AMINE(886362-07-8)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 886362-07-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Methoxy-1H-indazol-3-amine is used as a reactant in the preparation and structure-activity relationship of indazole arylsulfonamides. These compounds serve as allosteric CC-chemokine receptor 4 (CCR4) antagonists, which are important in the development of drugs targeting inflammatory and immune-related disorders. By modulating the activity of CCR4, indazole arylsulfonamides can potentially be used to treat various diseases, such as autoimmune diseases, allergies, and certain types of cancer, where the CCR4 receptor plays a significant role in the pathophysiology of the condition.

Synthesis

A mixture of 2-fluoro-6-(methyloxy)benzonitrile (8a) (10 g, 66 mmol) and hydrazine hydrate (9.63 mL, 198 mmol) in n-butanol (100 mL) was heated to reflux under nitrogen for 18 h. The reaction mixture was allowed to cool, water (300 mL) was added and the organic phase was removed. The solid in the aqueous phase was collected by filtration and dried in vacuo at 40 °C to give a white solid (0.6 g). The butanol phase was evaporated in vacuo and the residue and the aqueous mother liquors were combined and extracted using ethyl acetate (2 × 200 mL). The combined ethyl acetate extractions were dried (MgSO4) and evaporated in vacuo. The residue was dissolved in DCM and applied to a 100 g silica cartridge. This was eluted with cyclohexane (500 mL), cyclohexane ethyl acetate (1:1, 500 mL) and ethyl acetate (500 mL). The required fractions were combined and evaporated in vacuo to give 9a (9.92 g, 92%) as an off-white solid. MS ES + ve m/z 164 (M + H)+. 1H NMR δ (DMSO-d6) 11.35 (1H, s), 7.10 (1H, t, J = 8 Hz), 6.76 (1H, d, J = 8 Hz), 6.29 (1H, d, J = 8 Hz), 4.95 (2H, br s), 3.85 (3H, s).

InChI:InChI=1/C8H9N3O/c1-12-6-4-2-3-5-7(6)8(9)11-10-5/h2-4H,1H3,(H3,9,10,11)

Upstream product

• 94088-46-7 2-fluoro-6-methoxybenzonitrile 

Downstream Products

• 1240518-11-9 2-[4-(methyloxy)-1H-indazol-3-yl]-1H-isoindole-1,3(2H)-dione 
• 1240518-29-9 4-{[3-amino-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamide 
• 1240518-02-8 3-{[3-amino-4-(methyloxy)-1H-indazol-1-yl]methyl}-benzonitrile 
• 1240518-21-1 1-{[3,4-bis(methyloxy)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-amine 
• 1240518-71-1 1-{[3-fluoro-4-(methyloxy)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-amine 
• 1425941-49-6 C₂₄H₂₃ClN₄O₅S₂ 
• 1425941-50-9 C₂₄H₂₃ClN₄O₅S₂ 
• 1240517-13-8 N-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]tetrahydro-2-furancarboxamide 
• 1240516-51-1 N-[(3-{[3-{[(5-chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]tetrahydro-2H-pyran-4-carboxamide 
• 1240516-00-0 N¹-[(3-{[3-{[(5-chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]-N₂-methyl-D-alaninamide hydrochloride 
• 1240517-56-9 N₁-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]-2-methylalaninamide 
• 1425941-51-0 C₂₆H₂₈ClN₅O₄S₂*ClH 
• 1240515-96-1 (3R)-N-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]-3-morpholinecarboxamide hydrochloride 
• 1240515-97-2 (3S)-N-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]-3-morpholinecarboxamide hydrochloride 

Relevant articles and documents

COMPOUND, PREPARATION METHOD THEREFOR, AND USE THEREOF

The present disclosure provides a compound of formula I or a pharmaceutically acceptable salt, a solvate, or a prodrug thereof, wherein M is a monovalent alkali metal. The present disclosure also provides a method for preparing the compound or its pharmaceutically acceptable salt, solvate, or prodrug, and further provides a pharmaceutical composition containing the compound and its use in the preparation of a medicine, which can be used for the treatment of CCR4-mediated diseases.

Synthesis and structure-activity relationships of indazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists

A series of indazole arylsulfonamides were synthesized and examined as human CCR4 antagonists. Methoxy- or hydroxyl- containing groups were the more potent indazole C4 substituents. Only small groups were tolerated at C5, C6, or C7, with the C6 analogues being preferred. The most potent N3-substituent was 5-chlorothiophene-2-sulfonamide. N1 meta-substituted benzyl groups possessing an α-amino-3-[(methylamino)acyl]- group were the most potent N1-substituents. Strongly basic amino groups had low oral absorption in vivo. Less basic analogues, such as morpholines, had good oral absorption; however, they also had high clearance. The most potent compound with high absorption in two species was analogue 6 (GSK2239633A), which was selected for further development. Aryl sulfonamide antagonists bind to CCR4 at an intracellular allosteric site denoted site II. X-ray diffraction studies on two indazole sulfonamide fragments suggested the presence of an important intramolecular interaction in the active conformation.

INDAZOLE COMPOUNDS

Indazole compounds, processes for their preparation, pharmaceutical compositions containing such compounds and their use in therapy.

CC.CHEMOKINE RECEPTOR 4 ANTAGONISTS

Indazole compounds, processes for their preparation, pharmaceutical compositions containina such compounds and their use in the treatment of a disease or condition for which a CCR4 receptor antagonist is indicated.

Lead optimisation of the N1 substituent of a novel series of indazole arylsulfonamides as CCR4 antagonists and identification of a candidate for clinical investigation

Synthesis and preliminary SAR of the N1 substituent of a novel series of indazole sulfonamide chemokine receptor 4 (CCR4) antagonist is reported. Compound 7r was identified for further development.

INDAZOLYL-PYRIMIDINES AS KINASE INHIBITORS

Disclosed are compounds having the formula: or a salt thereof, wherein A, n, R1, R1A, and R2 are as defined herein, and methods of making and using the same.

3-[(Imidazolidin-2-yl)imino]indazole ligands with selectivity for the α2-adrenoceptor compared to the imidazoline I1 receptor

A series of 3-[(4,5-dihydroimidazolidin-2-yl)imino]indazoles has been synthesized as positional analogues of marsanidine, a highly selective α2-adrenoceptor ligand. Parent compound 4a and its 4-chloro (4c) and 4-methyl (4d) derivatives display α2-adrenoceptor affinity at nanomolar concentrations (Ki = 39.4, 15.9 and 22.6 nM, respectively) and relatively high α2/I1 selectivity ratios of 82, 115 and 690, respectively. Evidence was obtained that these compounds act as partial agonists at α2A-adrenoceptors. Compound 4d with intrinsic activity comparable with that of marsanidine, but lower than that of clonidine, elicited pronounced cardiovascular effects in anesthetized rats at doses as low as 0.01 mg/kg iv.

NOVEL COMPOUNDS

Indazole compounds, processes for their preparation, intermediates usable in these processes, pharmaceutical compositions containing such compounds and their use in therapy.