78775-33-4

Upstream product

• 50-00-0 formaldehyd 
• 20896-27-9 methyl 4-amino-5-chloro-2-methoxybenzoate 
• 78784-42-6 methyl 2-methoxy-4-(N-methyl-N-tosylamido)benzoate 
• 78775-32-3 methyl 5-chloro-2-methoxy-4-(N-methyl-N-tosylamido)benzoate 

Downstream Products

• 61694-98-2 5-chloro-2-methoxy-4-(methylamino)benzoic acid 
• 78775-18-5 5-Chloro-N-(1-cyclohexyl-pyrrolidin-2-ylmethyl)-4-dimethylamino-2-methoxy-benzamide 
• 82689-90-5 N-(1-Benzyl-pyrrolidin-2-ylmethyl)-5-chloro-2-methoxy-4-methylamino-benzamide 
• 70325-83-6 Emilace 
• 70325-83-6 N-((2S,3R)-1-Benzyl-2-methyl-pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylamino-benzamide 
• 82689-91-6 N-[2-(Benzyl-methyl-amino)-ethyl]-5-chloro-2-methoxy-4-methylamino-benzamide 
• 78784-39-1 5-Chloro-N-(1-ethyl-5-phenyl-pyrrolidin-2-ylmethyl)-2-methoxy-4-methylamino-benzamide 
• 78775-20-9 5-Chloro-N-(1-ethyl-pyrrolidin-3-yl)-2-methoxy-4-methylamino-benzamide 
• 73328-60-6 N-(1-Benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide 

Relevant academic research and scientific papers

Isolation of a highly functionalized Troeger's base derivative via a novel reaction

Heating a solution of methyl 5-chloro-4-[(ethoxyoxoacetyl) amino]-2-methoxybenz-oate, 3 in DMSO gave rise to the formation of the highly substitute.

Discovery of (R)-1-(3-((2-Chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1′-biphenyl]-2-ylcarbamate (TD-5959, GSK961081, Batefenterol): First-in-Class dual pharmacology multivalent muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD)

Through application of our multivalent approach to drug discovery we previously reported the first discovery of dual pharmacology MABA bronchodilators, exemplified by 1. Herein we describe the subsequent lead optimization of both muscarinic antagonist and β2 agonist activities, through modification of the linker motif, to achieve 24 h duration of action in a guinea pig bronchoprotection model. Concomitantly we targeted high lung selectivities, low systemic exposures and identified crystalline forms suitable for inhalation devices. This article culminates with the discovery of our first clinical candidate 12f (TD-5959, GSK961081, batefenterol). In a phase 2b trial, batefenterol produced statistical and clinically significant differences compared to placebo and numerically greater improvements in the primary end point of trough FEV1 compared to salmeterol after 4 weeks of dosing in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

THERAPEUTIC AGENT FOR RESPIRATORY DISEASE CONTAINING 4-HYDROXYPIPERIDINE DERIVATIVE AS ACTIVE INGREDIENT

An agent for preventing/treating respiratory diseases contains, as an active ingredient, a compound represented by following Formula (I): wherein A is a group represented by L-W [wherein L is a bond or CH2; and W is O, SOn (wherein n is 0 to 2), or -NR7-(wherein R7 is hydrogen or lower alkyl)]; each of G1 and G2 is (CH2)r (wherein r is 0 to 2), provided that when n is 1, G1 and G2 may be bridged by lower alkylene; Y is a lower alkylene or (substituted) benzylidene; Z is a bond or O, provided that when Z is a bond, Y may form a 5- or 6-membered ring with carbon on the benzene ring; R1 is, for example, NO2, a lower alkoxycarbonyl, (substituted) carbamoyl, (protected) hydroxyl group, (protected) carboxyl, or (protected) N-hydroxycarbamoyl; each of R2and R3 is hydrogen, halogen, (halogenated) lower alkyl, (halogenated) lower alkoxy or NO2; each of R4 and R5 is, for example, hydrogen, halogen, (halogenated) lower alkyl, (halogenated) lower alkoxy, CN, or lower alkylsulfonyl; and R6 is hydrogen or lower alkyl, a salt thereof or a solvate of them. It has excellent antitussive activity when used as an agent for preventing/treating respiratory diseases such as lung cancer, common cold syndrome, pulmonary tuberculosis, pneumonia, acute bronchitis or chronic bronchitis.