- AN IMPROVED PROCESS FOR THE PREPARATION OF ELVITEGRAVIR
-
The present invention relates to improved process for the preparation of elvitegravir (12), wherein the compound of formula (6) is protected with suitable protecting agents and further reacted with formula (9) in the presence of tetrakis(triphenylphosphin
- -
-
-
- HETEROCYCLIC UREA DERIVATIVES AND METHODS OF USE THEREOF
-
Compounds of formula (IA) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.
- -
-
Page/Page column 68
(2010/12/29)
-
- Quinolone carboxylic acids as a novel monoketo acid class of human immunodeficiency virus type 1 integrase inhibitors
-
Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto - enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited-marked antiretroviral activity. Here, we show the synthesis and the detailed structure - activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3,3- dimethylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nMin the strand transfer assay and an ED50 of 0.6 nMin the antiviral assay, and 6-(3-chloro-2-fluorobenzyl) -1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3- carboxylic acid 49, which had an IC50 of 7.2 nMand an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrasecatalyzed strand transfer processes than 3′-processing reactions, as is the case with the keto - enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.
- Sato, Motohide,Kawakami, Hiroshi,Motomura, Takahisa,Aramaki, Hisateru,Matsuda, Takashi,Yamashita, Masaki,Ito, Yoshiharu,Matsuzaki, Yuji,Yamataka, Kazunobu,Ikeda, Satoru,Shinkai, Hisashi
-
supporting information; experimental part
p. 4869 - 4882
(2010/03/02)
-
- DEUTERATED 4 -OXOQUINOLINE DERIVATIVES FOR THE TREATMENT OF HIV INFECTION
-
This invention relates to novel compounds that are 4-oxoquinoline derivatives and pharmaceutically acceptable salts thereof. More specifically, this invention relates to novel 4-oxoquinoline derivatives that are derivatives of elvitegravir. This invention
- -
-
Page/Page column 21-24
(2009/04/25)
-
- 6- (Heterocyclyl-substituted Benzyl) -4-Oxoquinoline Compound and Use Thereof as HIV Integrase Inhibitor
-
The present invention relates to a compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutical composition, an anti-HIV
- -
-
Page/Page column 33-34
(2008/12/08)
-
- Novel HIV-1 integrase inhibitors derived from quinolone antibiotics
-
The viral enzyme integrase is essential for the replication of human immunodeficiency virus type 1 (HIV-1) and represents a remaining target for antiretroviral drugs. Here, we describe the modification of a quinolone antibiotic to produce the novel integr
- Sato, Motohide,Motomura, Takahisa,Aramaki, Hisateru,Matsuda, Takashi,Yamashita, Masaki,Ito, Yoshiharu,Kawakami, Hiroshi,Matsuzaki, Yuji,Watanabe, Wataru,Yamataka, Kazunobu,Ikeda, Satoru,Kodama, Eiichi,Matsuoka, Masao,Shinkai, Hisashi
-
p. 1506 - 1508
(2007/10/03)
-
- COMBINATIONS COMPRISING A 4-ISOQUINOLONE DERIVATIVE AND ANTI-HIV AGENTS
-
The present invention relates to a combination therapy for treating an HIV infection or inhibiting integrase comprising (S)-6-(3-chloro-2-fluorobenzyl)-1-(1-hydroxymethyl-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ("Compound A"
- -
-
-
- STABLE CRYSTAL OF 4-OXOQUINOLINE COMPOUND
-
The present invention provides a crystal of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which shows a particular powder X-ray diffraction pattern of a characteristic diffractio
- -
-
-
- NOVEL 4-OXOQUINOLINE COMPOUND AND USE THEREOF AS HIV INTEGRASE INHIBITOR
-
Provision of a compound having an anti-HIV activity, particularly an integrase inhibitory activity.A 4-oxoquinoline compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the specification.The present invention also relates to a pharmaceutical composition containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier; an integrase inhibitor, an antiviral agent, anti-HIV agent and the like, which contains the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof as an active ingredient; an anti-HIV composition containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof, and one or more other kinds of anti-HIV activity substances as active ingredients; an anti-HIV agent containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof as an active ingredient, which is used for a multiple drug therapy with other anti-HIV agent(s), and the like.
- -
-
Page/Page column 112-113
(2008/06/13)
-
- 4-OXOQUINOLINE COMPOUNDS AND UTILIZATION THEREOF AS HIV INTEGRASE INHIBITORS
-
An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.
- -
-
Page/Page column 60
(2008/06/13)
-
