91247-71-1

Upstream product

• 67-56-1 methanol 
• 25413-27-8 3-(4-methoxy-phenyl)propionamide 
• 79-22-1 methyl chloroformate 
• 55-81-2 4-Methoxyphenethylamine 

Downstream Products

• 22246-04-4 7-methoxy-3,4-dihydro-2H-isoquinolin-1-one 
• 55-81-2 4-Methoxyphenethylamine 
• 4091-50-3 N-methylhomoanisylamine 
• 1187948-12-4 1-[2-methyl-7-(2-pyrrolidin-1-yl-ethoxy)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-cyclohexanol 
• 1187947-97-2 1-[2-methyl-7-(2-morpholin-4-yl-ethoxy)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-cyclohexanol 
• 1187948-69-1 1-[7-(tert-butyl-dimethyl-silanyloxy)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-cyclohexanol 
• 1187948-77-1 nicotinic acid 4-(1-hydroxy-cyclohexyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl ester 
• 1187948-35-1 1-(7-butoxy-2-isopropyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-cyclohexanol 
• 1187948-61-3 1-(2-methyl-7-phenoxy-1,2,3,4-tetrahydroisoquinolin-4-yl)-cyclohexanol 
• 1187948-74-8 carbonic acid ethyl ester 4-(1-hydroxycyclohexyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl ester 
• 1187948-72-6 4-(1-hydroxy-cyclohexyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ol 
• 1187948-41-9 2-isopropyl-1,2,3,4-tetrahydro-isoquinolin-7-ol 
• 913613-99-7 7-hydroxy-2-methyl-3,4-dihydroisoquinolin-1(2H)-one 
• 54893-23-1 7-methoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline 

Relevant academic research and scientific papers

Structure-Activity Relationship Studies of Pyrimidine-4-Carboxamides as Inhibitors of N-Acylphosphatidylethanolamine Phospholipase D

N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is regarded as the main enzyme responsible for the biosynthesis of N-acylethanolamines (NAEs), a family of bioactive lipid mediators. Previously, we reported N-(cyclopropylmethyl)-6-((S)-3-hydroxypyrrolidin-1-yl)-2-((S)-3-phenylpiperidin-1-yl)pyrimidine-4-carboxamide (1, LEI-401) as the first potent and selective NAPE-PLD inhibitor that decreased NAEs in the brains of freely moving mice and modulated emotional behavior [ Mock et al. Nat Chem. Biol., 2020, 16, 667-675 ]. Here, we describe the structure-activity relationship (SAR) of a library of pyrimidine-4-carboxamides as inhibitors of NAPE-PLD that led to the identification of LEI-401. A high-throughput screening hit was modified at three different substituents to optimize its potency and lipophilicity. Conformational restriction of an N-methylphenethylamine group by replacement with an (S)-3-phenylpiperidine increased the inhibitory potency 3-fold. Exchange of a morpholine substituent for an (S)-3-hydroxypyrrolidine reduced the lipophilicity and further increased activity by 10-fold, affording LEI-401 as a nanomolar potent inhibitor with drug-like properties. LEI-401 is a suitable pharmacological tool compound to investigate NAPE-PLD function in vitro and in vivo.

INHIBITORS OF N-ACYLPHOSPHATIDYLETHANOLAMINE PHOSPHOLIPASE D (NAPE-PLD)

The invention relates to a compound of the formula (I) as novel inhibitor of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD), and to use thereof for the prophylaxis or treatment of diseases associated with NAPE-PLD. wherein in a ring A, X1 is N, or CR4; X2 is N or CR5; X3 is N or CH; with the proviso that at least one of X1 and X3 is N.

Tyrosine Kinase Inhibitor And Uses Thereof

Disclosed is a compound of Formula (I) or a pharmaceutically acceptable salt, ester, or solvate thereof, or their stereoisomers, which can be used as tyrosine kinase inhibitor. Also disclosed is a method for preparing the compound, a pharmaceutical composition and a kit comprising the compound, and uses of the compound. The compound can be used as tyrosine kinase inhibitor, or can be used to reduce or inhibit activity of EGFR or mutant thereof, such as EGFR mutant comprising T790M mutation, in a cell, or to treat and/or prevent a disease associated with overactivity of EGFR, such as cancer.

BENZOXAZINONE DERIVATIVES AND ANALOGUES THEREOF AS MODULATORS OF TNF ACTIVITY

A series of substituted 3,4-dihydro-2H-.1,4-benzoxazin-3-one derivatives, and analogues thereof, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune

The importance of the 6- and 7-positions of tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor

Selective antagonism of the orexin 1 (OX1) receptor has been proposed as a potential mechanism for treatment of drug addiction. We have previously reported studies on the structure-activity relationships of tetrahydroisoquinoline-based antagonists. In this report, we elucidated the respective role of the 6- and 7-substitutions by preparation of a series of either 6-substituted tetrahydroisoquinolines (with no 7-substituents) or vice versa. We found that 7-substituted tetrahydroisoquinolines showed potent antagonism of OX1, indicating that the 7-position is important for OX1 antagonism (10c, Ke = 23.7 nM). While the 6-substituted analogs were generally inactive, several 6-amino compounds bearing ester groups showed reasonable potency (26a, Ke = 427 nM). Further, we show evidence that suggests several compounds initially displaying insurmountable antagonism at the OX1 receptor are competitive antagonists with slow dissociation rates.

Efficient synthesis of methyl carbamate via Hofmann rearrangement in the presence of TsNBr2

An efficient method has been developed for the synthesis of carbamates from the corresponding amides via the Hofmann rearrangement using N,N-dibromo-p-toluenesulfonamide (TsNBr2) in the presence of DBU in methanol. The reaction goes into completion in 10-20 min at 65 °C to produce the corresponding carbamate in excellent yield.

Activation of electrophilicity of stable Y-delocalized carbamate cations in intramolecular aromatic substitution reaction: Evidence for formation of diprotonated carbamates leading to generation of isocyanates

Although cations with three heteroatoms, such as monoprotonated guanidine and urea, are stabilized by Y-shaped conjugation and such Y-conjugated cations are sufficiently basic to be further protonated (or protosolvated) to dications in strongly acid media, only O-monoprotonated species have been detected in the case of carbamates even in magic acid. We found that the trifluoromethanesulfonic acid-catalyzed cyclization of arylethylcarbamates proceeds to afford dihydroisoquinolones in high yield. In strong acids, methyl carbamates are fully O-monoprotonated, and these monocations do not undergo cyclization even under heating. But, as the acidity of the reaction medium is further increased, the cyclization reaction of methyl phenethylcarbamates starts to proceed as a first-order reaction, with a linear relationship between rate and acidity. The sign and magnitude of the entropy of activation ΔS ? were found to be similar to those of other AAc1 reactions. These results strongly support the idea that further protonation of the O-protonated carbamates is involved in the cyclization, but the concentration of the dications is very low and suggests that the rate-determining step is dissociation of methanol from the diprotonated carbamate to generate protonated isocyanate, which reacts with the aromatic ring. Therefore, O-protonated carbamates are weak bases in sharp contrast to other Y-shaped monocations.

BICYCLIC INHIBITORS OF ALK

The present invention relates to compounds of formula (1) or pharmaceutical acceptable salts, wherein R1, X, Y, Z, A, B, G1, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as ALK and methods of treating diseases such as cancer.

NOVEL MONOAMINE RE-UPTAKE INHIBITOR

The present invention relates to novel compounds of Formula (I), their pharmaceutically acceptable derivatives, tautomeric forms, stereoisomers including R and S isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also rel

AZACYCLIC COMPOUNDS AS INHIBITORS OF SENSORY NEURONE SPECIFIC CHANNELS

Compounds of the formula (I), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents wherein: X is -N- or -CH-; n is from 0 to 3.