- Preparation method of remifenfloxacin intermediate
-
The invention discloses a preparation method of a remifenfloxacin intermediate, belongs to the technical field of drug synthesis, and solves the problems of long synthesis route, environmental unfriendliness, harsh reaction conditions and low yield of a remifenfloxacin key intermediate in the prior art. The preparation method of the remifenfloxacin intermediate as shown in the formula I comprises the following steps: reacting a compound as shown in a formula II with a compound as shown in a formula III or a salt thereof to generate a compound as shown in the formula I; the reaction formula is shown in the specification; and wherein X is halogen. The method is simple, easy and convenient to operate, short in route, high in yield, free of toxic oxidizing agents and catalytic hydrogenation, environmentally friendly and easier to industrialize, and only one step is needed.
- -
-
Paragraph 0049-0053
(2021/10/30)
-
- Preparation method of revefenacin intermediate
-
The invention discloses a preparation method of a revefenacin intermediate. The preparation method comprises the following steps: (1) carrying out a protective reaction on methylaminoacetaldehyde dimethyl acetal as shown in a formula I and a protecting gr
- -
-
Paragraph 0069; 0073; 0074; 0111-0132
(2021/07/17)
-
- Preparation methods of revefenacin intermediate and revefenacin
-
The invention relates to a synthesis method of a revefenacin intermediate, which specifically comprises the following steps: in a solvent, enabling piperidin-4-yl [1,1-biphenyl]-2-carbamate to react with methyl(2-oxyethyl) tert-butyl carbamate in the pres
- -
-
Paragraph 0055-0059
(2021/05/26)
-
- 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).
- Hughes, Adam D.,Chen, Yan,Hegde, Sharath S.,Jasper, Jeffrey R.,Jaw-Tsai, Sarah,Lee, Tae-Weon,McNamara, Alexander,Pulido-Rios, M. Teresa,Steinfeld, Tod,Mammen, Mathai
-
p. 2609 - 2622
(2015/04/14)
-
- PROCESS FOR PREPARING A BIPHENYL-2-YLCARBAMIC ACID
-
The invention provides a process of preparing an intermediate useful in the synthesis of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and a process of preparing a crystalline freebase of the ester.
- -
-
-
- Crystalline forms of a biphenyl compound
-
The invention provides crystalline forms of biphenyl-2-ylcarbamic acid 1-[2-({3-[2-(4-hydroxybenzylamino)ethylcarbamoyl]benzoyl}methylamino)ethyl]piperidin-4-yl ester, and pharmaceutically acceptable solvates thereof. The crystalline form can be a freebase (Form I or II), a salt such as a hemiedisylate salt or a heminapadisylate salt, or a solvate of a salt such as a heminapadisylate methanolate or a heminapadisylate ethanolate. The invention also provides pharmaceutical compositions comprising these crystalline compounds or prepared using these compounds; processes and intermediates for preparing the crystalline compounds; and methods of using these compounds to treat a pulmonary disorder.
- -
-
Page/Page column 16
(2010/11/30)
-
- Biphenyl compounds useful as muscarinic receptor antagonists
-
The invention provides compounds of formula I: wherein a, b, c, d, n, R1, R2, R3, R6, R7, W, and A are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
- -
-
Page/Page column 20
(2008/06/13)
-
- Biphenyl compounds useful as muscarinic receptor antagonists
-
The invention provides compounds of formula I: wherein a, b, c, p, W, A, X1, R1, R2, R3, R6, R7, and R8 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
- -
-
Page/Page column 26
(2008/06/13)
-
- Biphenyl compounds useful as muscarinic receptor antagonists
-
The invention provides compounds of formula I: wherein a, b, c, m, n, q, r, W, Z1, Ar1, Z2, Y, R1, R2, and R3 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
- -
-
Page/Page column 33
(2008/06/13)
-
- CRYSTALLINE FORMS OF A BIPHENYL COMPOUND
-
The invention provides crystalline forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and pharmaceutically acceptable solvates thereof. The crystalline form can be a freebase, or a salt such as a diphosphate, monosulfate or dioxalate salt. The invention also provides pharmaceutical compositions comprising these crystalline compounds or prepared using these compounds; processes and intermediates for preparing the crystalline compounds; and methods of using these compounds to treat a pulmonary disorder.
- -
-
Page/Page column 32
(2008/06/13)
-
- Biphenyl compounds useful as muscarinic receptor antagonists
-
The invention provides compounds of formula I: wherein a, b, c, m, s, t, W, Z, Ar, R1, R2, R3, R6, and R7 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
- -
-
Page/Page column 24
(2010/11/25)
-
- Biphenyl compounds useful as muscarinic receptor antagonists
-
This invention provides compounds of formula I: wherein a, b, c, m, p, r, R1, R2, R3, R4, R5, R6, W and X1 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
- -
-
Page/Page column 20
(2008/06/13)
-
- Biphenyl compounds useful as muscarinic receptor antagonists
-
This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, r, R1, R2, R3, R4, R5, R6, R7, and W are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
- -
-
Page/Page column 18
(2008/06/13)
-
- Biphenyl compounds useful as muscarinic receptor antagonists
-
This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, s, t, W, Ar1, R1, R2, R3, R4, R6, R7, and R8 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
- -
-
Page/Page column 20
(2008/06/13)
-
- Biphenyl compounds useful as muscarinic receptor antagonists
-
This invention provides compounds of formula I: wherein a, b, c, m, p, s, t, W, Ar1, X1, R1, R2, R3, R4, R6, and R7 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
- -
-
Page/Page column 20
(2010/02/13)
-
- Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity
-
The invention is directed to compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7a, R7b, W, G1, G2, a, b, c, d and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
- -
-
Page/Page column 41
(2008/06/13)
-
- Biphenyl derivatives
-
This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
- -
-
Page/Page column 39
(2008/06/13)
-