Abstract: The invention is directed to a method for treatment of viral infections, particularly HIV infection. The method involves administering compounds which are substituted (3S,11aR)-N-[(2,4-difluorophenyl)methyl]-6-oxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamides of formula (I).
Type:
Grant
Filed:
August 5, 2015
Date of Patent:
July 18, 2017
Assignees:
SHIONOGI & CO., LTD., VIIV HEALTHCARE COMPANY
Inventors:
Brian Alvin Johns, Jason Gordon Weatherhead, Toshikazu Hakogi, Yasunori Aoyama
Abstract: The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
Type:
Application
Filed:
February 8, 2017
Publication date:
May 25, 2017
Applicants:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian A. JOHNS, Takashi KAWASUJI, Teruhiko TAISHI, Yoshiyuki TAODA
Abstract: The present invention relates to the preparation of (4R,12aS)-N-(2,4-difluorobenzyl)-7-methoxy-4 -methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1?,2?:4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide of the formula VIIa:
Type:
Grant
Filed:
July 28, 2015
Date of Patent:
May 9, 2017
Assignee:
ViiV Healthcare Company
Inventors:
Steven N. Goodman, Huan Wang, Douglas Mans, Matthew Kowalski
Abstract: The present invention is to provide a novel compound (I) shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
Type:
Application
Filed:
October 11, 2016
Publication date:
February 2, 2017
Applicants:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian A. JOHNS, Takashi KAWASUJI, Teruhiko TAISHI, Yoshiyuki TAODA
Abstract: The present invention relates to combinations of compounds comprising HIV integrase inhibitors and other therapeutic agents. Such combinations are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
Abstract: The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z1 is NR1; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to forma polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
Type:
Application
Filed:
June 29, 2016
Publication date:
October 20, 2016
Applicants:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian A. JOHNS, Takashi KAWASUJI, Teruhiko TAISHI, Yoshiyuki TAODA
Abstract: The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
Type:
Application
Filed:
March 31, 2016
Publication date:
July 21, 2016
Applicants:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian A. JOHNS, Takashi KAWASUJI, Teruhiko TAISHI, Yoshiyuki TAODA
Abstract: The invention is a process for the preparation of a compound of the following formula (I): wherein R is —CHO, —CH(OH)2 or —CH(OH)(OR4); P1 is H or a hydroxyl protecting group; P3 is H or a carboxy protecting group; R3 is H, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted cycloalkyl, etc.; Rx is H, halogen or R2—X—NR1—C(O)—; etc. as defined in the specification. The compounds are useful as intermediates in synthesizing compounds having HIV integrase inhibitory activity.
Type:
Grant
Filed:
November 10, 2015
Date of Patent:
June 14, 2016
Assignees:
SHIONOGI & CO., LTD., ViiV HEALTHCARE COMPANY
Abstract: The present invention is to provide a novel compound (I) shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
Type:
Application
Filed:
January 20, 2016
Publication date:
May 19, 2016
Applicants:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian Alvin Johns, Takashi Kawasuji, Teruhiko Taishi, Yoshiyuki Taoda
Abstract: A synthesis approach providing an early ring attachment via a bromination to compound l-l yielding compound II-Il, whereby a final product such as AA can be synthesized. In particular, the 2,4-difluorophenyl-containing sidechain is attached before creation of the additional ring Q.
Abstract: The present invention is directed to a class of substituted pyrido[1?2?:4,5]pyrazino[1,2-a]-pyrimidines useful as intermediates in the production of anti-HIV agents. The compounds have the formula (I-24b): wherein Re is one or two halogen; Rz is C1-8alkyl; Rz is hydrogen, C3-6cycloalkyl, heterocyclyl, or C1-8alkyl optionally substituted with hydroxy, C3-6cycloalkyl, alkoxy, heterocyclyl, heteroaryl, C6-14aryl, or amino, wherein said amino may be optionally substituted with —C(O)C1-8alkyl or C1-8alkyl; and P1 is C6-14arylC1-8alkyl; or a pharmaceutically acceptable salt thereof.
Type:
Grant
Filed:
April 30, 2015
Date of Patent:
March 1, 2016
Assignees:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian A. Johns, Takashi Kawasuji, Teruhiko Taishi, Yoshiyuki Taoda
Abstract: A synthesis approach providing an early ring attachment via a bromination to compound 1-1 yielding compound II-II, whereby a final product such as AA can be synthesized. In particular, the 2,4-difluorophenyl-containing sidechain is attached before creation of the additional ring Q.
Type:
Grant
Filed:
May 8, 2014
Date of Patent:
January 26, 2016
Assignees:
SHIONOGI & CO., LTD., ViiV Healthcare Company
Abstract: The compounds are intermediates in the preparation of therapeutic agents useful in the treatment of viral infections, particularly HIV infection. The compounds are (3S,11aR)-6-[(phenylmethyl)oxy]-3-methyl-2,3,11,11a-tetrahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-5,7-dione of the formula P-9 and/or (3S,11aR)-6-[(phenylmethyl)oxy]-8-bromo-3-methyl-2,3,11,11a-tetrahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-5,7-dione of the formula P-10.
Type:
Grant
Filed:
March 17, 2015
Date of Patent:
September 15, 2015
Assignees:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian Alvin Johns, Jason Gordon Weatherhead, Toshikazu Hakogi, Yasunori Aoyama
Abstract: The present invention relates to processes for the preparation of (4R,12aS)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1?,2?:4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid by contacting a pyridinone carboxylic acid aldehyde with (3R)-3-amino-1-butanol.
Type:
Grant
Filed:
October 14, 2014
Date of Patent:
September 1, 2015
Assignee:
VIIV HEALTHCARE COMPANY
Inventors:
Steven N. Goodman, Huan Wang, Douglas Mans, Matthew Kowalski
Abstract: The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
Type:
Grant
Filed:
March 14, 2014
Date of Patent:
June 9, 2015
Assignees:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian A. Johns, Takashi Kawasuji, Teruhiko Taishi, Yoshiyuki Taoda
Abstract: The compounds are therapeutic agents useful in the treatment of viral infections, particularly HIV infection. The compounds are substituted (3S, 11aR)-N-[(2,4 -difluorophenyl)methyl]-6-oxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamides of formula (I).
Type:
Grant
Filed:
May 21, 2014
Date of Patent:
April 21, 2015
Assignees:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian Alvin Johns, Jason Gordon Weatherhead, Toshikazu Hakogi, Yasunori Aoyama
Abstract: The compounds are intermediates in the preparation of therapeutic agents useful in the treatment of viral infections, particularly HIV infection. The compounds are 2-(2-hydroxy-2-phenylethyl)-3-[(phenylmethyl)oxy]-4H-pyran-4-one of the formula P-3 and/or 2-[(E)-2-phenylethenyl]-3-[(phenylmethyl)oxy]-4H-pyran-4-one of the formula P-4.
Type:
Grant
Filed:
May 20, 2014
Date of Patent:
March 17, 2015
Assignees:
Shionogi & Co., Ltd., ViiV Healthcare Company
Inventors:
Brian Alvin Johns, Jason Gordon Weatherhead, Toshikazu Hakogi, Yasunori Aoyama
Abstract: The present invention features a process for the preparation of 4-oxo-3-[(phenylmethyl)oxy]-4-H-pyran-2-carboxylic acid, an intermediate useful in the synthesis of HIV integrase inhibitors. The process involves (a) treating a compound of formula P-2 with lithium bis(trimethylsilyl)amide and benzaldehyde to form a compound of formula P-3, (b) treating the compound of formula P-3 with triethylamine and methanesulfonyl chloride followed by N-methyl-2-pyrrolidone and 1,8-diazabicyclo[5.4.0]undec-7-ene to form a compound of formula P-4, and (c) treating the compound of formula P-4 with RuCl3 and NaIO4 to form the compound of formula P-5.