18222-17-8

Usage

Uses

Used in Pharmaceutical Industry:
3-Methyl-5-nitroisoquinoline is used as a key intermediate in the synthesis of pharmaceuticals for its ability to form heterocyclic compounds, which are integral in creating new drug molecules with potential therapeutic applications.
Used in Agrochemical Development:
In the agrochemical industry, 3-Methyl-5-nitroisoquinoline is utilized as a starting material for the preparation of various agrochemicals, contributing to the development of new compounds with pesticidal or herbicidal properties.
Used in Organic Synthesis:
3-Methyl-5-nitroisoquinoline is employed as a versatile building block in organic synthesis, enabling the creation of a wide range of organic compounds for various applications, including but not limited to, the development of new materials and specialty chemicals.
Used in Research and Development:
3-METHYL-5-NITROISOQUINOLINE is also used in research and development settings for studying its chemical properties and potential applications, including its reactivity and behavior in different chemical reactions, which can lead to the discovery of new synthetic pathways and compounds.

InChI:InChI=1/C10H8N2O2/c1-7-5-9-8(6-11-7)3-2-4-10(9)12(13)14/h2-6H,1H3

Upstream product

• 1125-80-0 3-methylisoquinoline 
• 60912-31-4 benzyl-(2,2-dimethoxy-1-methyl-ethyl)-amine 
• 100-46-9 benzylamine 
• 7664-93-9 sulfuric acid 

Downstream Products

• 54410-17-2 3-methyl-isoquinolin-5-ylamine 
• 1221443-94-2 (R)-1-(7-chloro-2,2-bis(fluoromethyl)-chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea 

Relevant academic research and scientific papers

Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (a-1165442): A temperature-neutral transient receptor potential vanilloid-1 (trpv1) antagonist with analgesic efficacy

The synthesis and characterization of a series of selective, orally bioavailable 1-(chroman-4-yl)urea TRPV1 antagonists is described. Whereas first-generation antagonists that inhibit all modes of TRPV1 activation can elicit hyperthermia, the compounds disclosed herein do not elevate core body temperature in preclinical models and only partially block acid activation of TRPV1. Advancing the SAR of this series led to the eventual identification of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442, 52), an analogue that possesses excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents.

Asymmetric synthesis of a TRPV1 antagonist via tert -butanesulfinamide- directed reductive amination with a chromanone

An expedient asymmetric synthesis of TRPV1 antagonist 1 has been developed and demonstrated on multikilogram scale. The enabling route to 1 is detailed herein and characterized by the following key transformations: an aldol-cyclodehydration sequence to install the chromanone, and an auxiliary-mediated diastereoselective reductive amination.

TRPV1 ANTAGONISTS

Disclosed herein are compounds of Formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

TRPV1 ANTAGONISTS

Disclosed herein are compounds of formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS

The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).

In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists

The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino) benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.

UREA DERIVATIVES

Compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein P, P', W, R1, R2, n, p, q, r, s and t are as defined in the specification, processes for preparing such compounds, pharmaceutical composition

UREA COMPOUNDS ACTIVE AS VANILLOID RECEPTOR ANTAGONISTS FOR THE TREATMENT OF PAIN

Certain compounds of formula (I): or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, P, P', n, p, q, r and s are as defined in the specification, a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds in medicine.

AMINO-HETEROCYCLES AS VR-1 ANTAGONISTS FOR TREATING PAIN

the present invention provides a compound of formula (I): wherein V represents NR5, O, S, SO or S(O)2; W and X each independently represent CH or N; Y represents N, CH or C-Ar2, with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C-Ar2, with the proviso that when Y is N or CH then Z is C-Ar2, and with the further proviso that when Y is C-Ar2 then Z is CH; Ar1 represents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Ar2 represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R1 represents halogen, hydroxy, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, haloC1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, hydroxyC1-6alkoxy, C3-7cycloalkyl, C3-7cycloalkoxy, C3-5cycloalkylC1-4alkyl, cyano, nitro, SR6, SOR6, SO2R6, COR6, NR3COR6, CONR3R4, NR3SO2R6, SO2NR3R4, -(CH2)mcarboxy, esterified -(CH2)mcarboxy or -(CH2)mNR3R4; R2 represents hydrogen, halogen, hydroxy, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy, haloC1-6alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; R3 and R4 are each independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl or fluoroC1-6alkyl; or R3 and R4 and the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or C1-4alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O)2, or NR5; R5 represents hydrogen, C1-4alkyl, hydroxyC1-4alkyl or C1-4alkoxyC1-4alkyl; R6 represents hydrogen, C1-6alkyl, fluoroC1-6alkyl, C3-7cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it.

Spirooxazines and use thereof in the field of ophthalmic optics

The invention relates to photochromic compounds of general formula: STR1 in which: Ra and Rb denote hydrogen; alkyl; OR, SR, COR or COOR where R denotes hydrogen, alkyl, aryl or heteroaryl; a group NR1 R2 where R1 R2 denotes hydrogen, C4 -C7 alkyl or cycloalkyl, aryl, or form with the nitrogen a C4 -C7 heterocycle; NO2, CN, SCN or a halogen; a group SO3 R' where R' denotes hydrogen or an alkali metal; a mono- or polyhaloalkyl; m denotes an integer from 1 to 4 and n is equal to 1 or 2; Cy denotes an aromatic ring or an aromatic or non-aromatic heterocycle; Rc denotes an alkyl, allyl, phenyl or arylalkyl group which is mono- or disubstituted with alkyl, alkoxy or NO2 ; an alicyclic, an aliphatic hydrocarbon containing one or more hetero atoms; Rd, Re, Rf and Rg denote hydrogen, alkyl, alkoxy or thioalkyl or form in pairs a 4- to 7-membered cycloalkyl possibly containing hetero atoms which are optionally condensed with an aromatic ring; Rh denotes hydrogen or forms with Rd a 5- or 6-membered cycloalkyl; and the use thereof in ophthalmic optics.