# US 10,870,661 B2 · Nitrogen-containing tricyclic derivatives having HIV replication inhibitory activity > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,870,661 B2 - Document ID: US10870661B2 - Status: Granted - Kind: B2 - Application number: 16/665,231 - Filed: 2019-10-28 - Published: 2020-02-20 - Granted: 2020-12-22 - Earliest claimed: 2015-05-29 - Assignees: Shionogi & Co., Ltd. - Applicants: Shionogi & Co., Ltd. - Inventors: Yoshinori Tamura; Shuichi Sugiyama; Akira Matsumura; Toshiyuki Akiyama; Yutaka Tomida - Web page: https://patentgrep.com/patent/US10870661B2 ## CPC - C07D 513/06: Peri-condensed systems - A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems - A61K 31/554: having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem - A61P 31/18: for HIV - C07D 487/06: Peri-condensed systems - Y02P 20/55: Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS ## Abstract The present invention provides a novel compound having antiviral activity, especially HIV replication inhibitory activity and a medicament containing the same. The compound represented by the formula: wherein A3 is CR3A, CR3AR3B, N or NR3C; R3A, R3B, R4A and R4B are each independently a hydrogen atom, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted non-aromatic carbocyclyl; R3C is a hydrogen atom, substituted or unsubstituted alkyl, or substituted or unsubstituted non-aromatic carbocyclyl; ring T1 is substituted or unsubstituted nitrogen-containing non-aromatic heterocycle; R1 is a hydrogen atom, halogen, cyano, or substituted or unsubstituted alkyl; R2 is each independently substituted or unsubstituted alkyl or the like: n is 1 or 2; R3 is substituted or unsubstituted aromatic carbocyclyl or the like; R4 is a hydrogen atom or a carboxy protecting group. ## Claims ### Claim 1 A compound of formula (I-1-1B) or a pharmaceutically acceptable salt thereof, wherein R1 is alkyl or halogen; R2 is alkyloxy; R3 is aromatic carbocyclyl optionally substituted with halogen, alkyl and/or alkyloxy, non-aromatic carbocyclyl optionally substituted with halogen, alkyl and/or alkyloxy, aromatic heterocyclyl optionally substituted with halogen alkyl and/or alkyloxy, or non-aromatic heterocyclyl optionally substituted with halogen, alkyl and/or alkyloxy, the aromatic carbocyclyl is phenyl, the non-aromatic carbocyclyl is a cyclic saturated hydrocarbon group or a cyclic unsaturated non-aromatic hydrocarbon, which is C3 to C16 monocyclic or C8 to C13 polycyclic having two or more rings, wherein non-aromatic carbocyclyl which is polycyclic having two or more rings may be a fused cyclic group where a non-aromatic carbocyclyl, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the aromatic carbocyclyl, the non-aromatic carbocyclyl may be a group having a bridge or a group to form a spiro ring, the aromatic heterocyclyl is 5 or 6-memebered monocyclic or 9 or 10-membered polycyclic having two rings, containing one or more and same or different heteroatoms selected from O, S, and N, the non-aromatic heterocyclyl is 5 or 6-membered monocyclic or 8 to 20 membered polycyclic having two or more rings, containing one or more and same or different heteroatoms arbitrarily selected from O, S and N, wherein non-aromatic heterocyclyl which is polycyclic having two or more rings may be a fused cyclic group where a non-aromatic heterocyclyl, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the aromatic carbocyclyl, non-aromatic carbocyclyl, and/or aromatic heterocyclyl, and the non-aromatic heterocyclyl may be a group having a bridge by alkylene, or a group to form a Spiro ring with alkylene; R4 is hydrogen; R3A is hydrogen or halogen; R4A is alkyl optionally substituted with cyano, halogen, hydroxy or alkyloxy, halogen, alkynyl, or 3-membered non-aromatic carbocyclyl; Ra is hydrogen, alkyl, haloalkyl, aminoalkyl, alkylamino dialkylamino alkyl, alkyloxyalkyl, alkylsulfonyl, or haloalkylsulfonyl; Rb is each independently hydrogen, alkyl, haloalkyl, or alkyloxyalkyl; Rc is each independently hydrogen, alkyl, haloalkyl, or alkyloxyalkyl. ### Claim 2 (depends on 1) The compound or pharmaceutically acceptable salt according to claim 1, wherein R3 is selected from the group consisting of ### Claim 3 (depends on 1) The compound or pharmaceutically acceptable salt according to claim 1, wherein R4A is alkyl. ### Claim 4 (depends on 1) The compound or pharmaceutically acceptable salt according to claim 1, wherein R1 is methyl; R2 is tert-butyloxy; R3 is selected from the group consisting of R4 is hydrogen; R3A is hydrogen; R4A is methyl; Ra is hydrogen, alkyl, haloalkyl, aminoalkyl, alkylamino alkyl, dialkylamino alkyl, alkyloxyalkyl, alkylsulfonyl, or haloalkylsulfonyl; Rb is each independently hydrogen, alkyl, haloalkyl, or alkyloxyalkyl; and Rc is each independently hydrogen, alkyl, haloalkyl, or alkyloxyalkyl. ### Claim 5 (depends on 1) A pharmaceutical composition, comprising: the compound or pharmaceutically acceptable salt according to claim 1 in an effective amount; and a pharmaceutically acceptable carrier. ### Claim 6 (depends on 5) The pharmaceutical composition according to claim 5, wherein the effective amount of the compound or pharmaceutically acceptable salt is an effective amount having anti-virus activity. ### Claim 7 (depends on 5) The pharmaceutical composition according to claim 5, wherein the effective amount of the compound or pharmaceutically acceptable salt is an effective amount having anti-HIV activity. ### Claim 8 (depends on 1) A method of treating or preventing a HIV infectious disease, comprising: administering the compound or pharmaceutically acceptable salt according to claim 1 to a patient in need thereof. ### Claim 9 A compound of formula (I-1-1B) or a pharmaceutically acceptable salt thereof, wherein R1 is alkyl or halogen; R2 is alkyloxy; R3 is aromatic carbocyclyl optionally substituted with halogen, alkyl and/or alkyloxy, non-aromatic carbocyclyl optionally substituted with halogen, alkyl and/or alkyloxy, aromatic heterocyclyl optionally substituted with halogen, alkyl and/or alkyloxy, or non-aromatic heterocyclyl optionally substituted with halogen, alkyl and/or alkyloxy, the aromatic carbocyclyl is phenyl, the non-aromatic carbocyclyl is a cyclic saturated hydrocarbon group or a cyclic unsaturated non-aromatic hydrocarbon, which is C3 to C16 monocyclic or C8 to C13 polycyclic having two or more rings, wherein non-aromatic carbocyclyl which is polycyclic having two or more rings may be a fused cyclic group where a non-aromatic carbocyclyl, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the aromatic carbocyclyl, the non-aromatic carbocyclyl may be a group having a bridge or a group to form a spiro ring, the aromatic heterocyclyl is 5 or 6-memebered monocyclic or 9 or 10-membered polycyclic having two rings, containing one or more and same or different heteroatoms selected from O, S and N, the non-aromatic heterocyclyl is 5 or 6-membered monocyclic or 8 to 20 membered polycyclic having two or more rings, containing one or more and same or different heteroatoms arbitrarily selected from O, S and N, wherein non-aromatic heterocyclyl which is polycyclic having two or more rings may be a fused cyclic group where a non-aromatic heterocyclyl which is monocyclic or polycyclic having two or more rings, is fused with a ring of the aromatic carbocyclyl non-aromatic carbocyclyl, and/or aromatic heterocyclyl, and the non-aromatic heterocyclyl may be a group having a bridge by alkylene, or a group to form a spiro ring with alkylene; R4 is hydrogen; R3A is hydrogen or halogen; R4A is alkyl optionally substituted with cyano, halogen, hydroxy or alkyloxy, halogen, alkynyl, or 3-membered non-aromatic carbocyclyl; Ra is each independently aromatic heterocyclyl optionally substituted with one or more groups selected from Substituent Group E or non-aromatic heterocyclyl optionally substituted with one or more groups selected from Substituent Group E, the aromatic heterocyclyl is 5 or 6-memebered monocyclic or 9 or 10-membered polycyclic having two rings, containing one or more and same or different heteroatoms selected from O, S and N, the non-aromatic heterocyclyl is 5 or 6-membered monocyclic or 8 to 16 membered polycyclic having two or more rings, containing one or more and same or different heteroatoms arbitrarily selected from O, S and N, and the Substituent Group E is alkyl, halogen, alkyloxy, dialkylamino alkyloxy, alkylamino alkyloxy, amino alkyloxy, non-aromatic heterocyclylalkyl oxy, non-aromatic heterocyclyloxy optionally substituted with alkyl and/or oxo, non-aromatic heterocyclyl optionally substituted with alkyl and/or oxo, dialkylamino alkyl, alkylamino alkyl, amino alkyl, non-aromatic heterocyclylalkyl, and aromatic heterocyclyl optionally substituted with alkyl, wherein the aromatic heterocyclyl is 5 or 6-memebered monocyclic or 9 or 10-membered polycyclic having two rings, containing one or more and same or different heteroatoms selected from O, S and N, and the non-aromatic heterocyclyl is 3 to 8-membered monocyclic containing one or more and same or different heteroatoms arbitrarily selected from O, S and N; Rb is each independently hydrogen, alkyl, haloalkyl, or alkyloxyalkyl; and Rc is each independently hydrogen, alkyl, haloalkyl, or alkyloxyalkyl. ### Claim 10 (depends on 9) The compound or pharmaceutically acceptable salt according to claim 9, wherein the Substituent Group E includes alkyl, halogen, alkyloxy, dialkylamino alkyloxy, and alkylamino alkyloxy. ### Claim 11 (depends on 9) The compound or pharmaceutically acceptable salt according to claim 9, wherein R1 is methyl; R2 is tert-butyloxy; R3 is selected from the group consisting of R4 is hydrogen; R3A is hydrogen; R4A is methyl; Ra is each independently aromatic heterocyclyl optionally substituted with one or more groups selected from Substituent Group E or non-aromatic heterocyclyl optionally substituted with one or more groups selected from Substituent Group E; wherein Substituent Group E is alkyl, halogen, alkyloxy, dialkylamino alkyloxy, and alkylamino alkyloxy; Rb is each independently hydrogen, alkyl, haloalkyl, or alkyloxyalkyl; and Rc is each independently hydrogen, alkyl, haloalkyl, or alkyloxyalkyl. ### Claim 12 (depends on 9) The compound or pharmaceutically acceptable salt according to claim 9, wherein R3 is selected from the group consisting of ### Claim 13 (depends on 9) The compound or pharmaceutically acceptable salt according to claim 9, wherein R4A is alkyl. ### Claim 14 (depends on 9) A pharmaceutical composition, comprising: the compound or pharmaceutically acceptable salt according to claim 9 in an effective amount; and a pharmaceutically acceptable carrier. ### Claim 15 (depends on 14) The pharmaceutical composition according to claim 14, wherein the effective amount of the compound or pharmaceutically acceptable salt is an effective amount having anti-virus activity. ### Claim 16 (depends on 14) The pharmaceutical composition according to claim 14, wherein the effective amount of the compound or pharmaceutically acceptable salt is an effective amount having anti-HIV activity. ### Claim 17 (depends on 9) A method of treating or preventing an HIV infectious disease, comprising: administering the compound or pharmaceutically acceptable salt according to claim 9 to a patient in need thereof. ### Claim 18 (depends on 1) The compound or pharmaceutically acceptable salt according to claim 1, wherein R1 is methyl; R2 is tert-butyloxy; R3 is selected from the group consisting of R4 is hydrogen; R3A is hydrogen; R4A is methyl; Ra is hydrogen, alkyl, haloalkyl, alkylamino alkyl, or dialkylamino alkyl; Rb is each independently hydrogen; and Rc is each independently hydrogen. ### Claim 19 (depends on 18) The compound or pharmaceutically acceptable salt according to claim 18, wherein Ra is alkyl, haloalkyl, alkylamino alkyl, or dialkylamino alkyl. ### Claim 20 (depends on 9) The compound or pharmaceutically acceptable salt according to claim 9, wherein R1 is methyl; R2 is tert-butyloxy; R3 is selected from the group consisting of R4 is hydrogen; R3A is hydrogen; R4A is methyl; Ra is aromatic heterocyclyl optionally substituted with at least one group selected from the Substituent Group E, wherein the aromatic heterocyclyl is 6-memebered monocyclic containing one or two N, and the Substituent Group E is alkyl, halogen, alkyloxy, dialkylamino alkyloxy, alkylamino alkyloxy, dialkylamino alkyl, or alkylamino alkyl; Rb is each independently hydrogen; and Rc is each independently hydrogen. ### Claim 21 (depends on 20) The compound or pharmaceutically acceptable salt according to claim 20, wherein Ra is pyrimidinyl optionally substituted with one group selected from the Substituent Group E, and the Substituent Group E is alkyl, halogen, alkyloxy, dialkylamino alkyloxy, alkylamino alkyloxy, dialkylamino alkyl, or alkylamino alkyl.