公开(公告)号：US20210253553A1

公开(公告)日：2021-08-19

申请号：US17240792

申请日：2021-04-26

Applicant: Insilico Medicine IP Limited

Inventor： Aleksandrs Zavoronkovs ,  Vladimir Aladinskiy ,  Aleksandr Aliper

IPC: C07D401/12 ,  C07D401/14

Abstract: A TLR9 inhibitor includes a compound of general formula (I): wherein the meanings of the variables are explained in the specification, or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof. A pharmaceutical composition can include compounds of the invention, which can be used in a method for inhibiting TLR9 activity in vitro or in vivo. The method can be performed by administering the compound to a subject to inhibit TLR9 activity, which can be used to treat a disease or disorder associated with TLR9.

公开(公告)号：US11008303B2

公开(公告)日：2021-05-18

申请号：US16889462

申请日：2020-06-01

Applicant: Insilico Medicine IP Limited

Inventor： Aleksandrs Zavoronkovs ,  Vladimir Aladinskiy ,  Aleksandr Aliper

IPC: C07D401/12 ,  C07D401/14

Abstract: A method for inhibiting TLR9 includes contacting the TLR9 with compound of general formula (I): wherein the meanings of the variables are explained in the specification, or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof. A pharmaceutical composition can include compounds of the invention, which can be used in a method for inhibiting TLR9 activity in vitro or in vivo. The method can be performed by administering the compound to a subject to inhibit TLR9 activity, which can be used to treat a disease or disorder associated with TLR9.

公开(公告)号：US20240152763A1

公开(公告)日：2024-05-09

申请号：US18538870

申请日：2023-12-13

Applicant: INSILICO MEDICINE IP LIMITED

Inventor： Aleksandr Aliper ,  Aleksandrs Zavoronkovs ,  Alexander Zhebrak ,  Daniil Polykovskiy ,  Maksim Kuznetsov ,  Yan Ivanenkov ,  Mark Veselov ,  Vladimir Aladinskiy ,  Evgeny Putin ,  Yuriy Volkov ,  Arip Asadulaev

IPC: G06N3/092 ,  G06N3/0455 ,  G06N3/0475 ,  G06N3/084

CPC classification number: G06N3/092 ,  G06N3/0455 ,  G06N3/0475 ,  G06N3/084

Abstract: The proposed model is a Variational Autoencoder having a learnable prior that is parametrized with a Tensor Train (VAE-TTLP). The VAE-TTLP can be used to generate new objects, such as molecules, that have specific properties and that can have specific biological activity (when a molecule). The VAE-TTLP can be trained in a way with the Tensor Train so that the provided data may omit one or more properties of the object, and still result in an object with a desired property.

公开(公告)号：US20240092764A1

公开(公告)日：2024-03-21

申请号：US18240293

申请日：2023-08-30

Applicant: Insilico Medicine IP Limited

Inventor： Aleksandr Aliper ,  Vladimir Aladinskiy ,  Aleksandrs Zavoronkovs

IPC: C07D405/04 ,  A61K31/4164 ,  A61K31/4439 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04 ,  C07D491/048

CPC classification number: C07D405/04 ,  A61K31/4164 ,  A61K31/4439 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04 ,  C07D491/048

Abstract: A TNIK and/or MAP4K4 kinase inhibitor can include: Formula A, derivative, prodrug, salt, stereoisomer, tautomer polymorph, or solvate thereof, or having chirality at any chiral center,






wherein: ring 1 is an aromatic ring with or without hetero atoms; ring 2 is a hetero aromatic ring; ring 3 includes at least one hetero aromatic ring and optionally at least one cycloaliphatic ring fused with the at least one hetero aromatic ring; ring 4 is an aromatic ring with or without hetero atoms; Y is a bond or a linker; Y1 is a linker; each n is independently 0, 1, or 2; each o is independently 0, 1, 2, 3, 4, or 5; each R1, R6, R11, and R12 is independently a substituent; and RA is a ring structure, straight aliphatics, or branched aliphatics, which can be substituted or unsubstituted, any with or without hetero atoms.

公开(公告)号：US11739078B2

公开(公告)日：2023-08-29

申请号：US16796879

申请日：2020-02-20

Applicant: INSILICO MEDICINE IP LIMITED

Inventor： Aleksandr Aliper ,  Vladimir Aladinskiy ,  Aleksandrs Zavoronkovs

IPC: A61K31/4439 ,  A61K31/506 ,  A61K31/4164 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D403/04 ,  C07D413/04 ,  C07D401/14 ,  C07D401/04 ,  C07D471/04 ,  C07D491/048 ,  C07D403/14 ,  C07D417/04

CPC classification number: C07D405/04 ,  A61K31/4164 ,  A61K31/4439 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04 ,  C07D491/048

Abstract: A method of inhibiting TNIK and/or MAP4K4 kinase can include: contacting the kinase with a compound of Formula A,






wherein: ring 1 is an aromatic ring with or without hetero atoms; ring 2 is a hetero aromatic ring; ring 3 includes at least one hetero aromatic ring and optionally at least one cycloaliphatic ring fused with the at least one hetero aromatic ring; ring 4 is an aromatic ring with or without hetero atoms; Y is a bond or a linker; Y1 is a linker; each n is independently 0, 1, or 2; each o is independently 0, 1, 2, 3, 4, or 5; each R1, R6, R11, and R12 is independently a substituent; and RA is a ring structure, straight aliphatics, or branched aliphatics, which can be substituted or unsubstituted, any with or without hetero atoms.

公开(公告)号：US20210057050A1

公开(公告)日：2021-02-25

申请号：US17000109

申请日：2020-08-21

Applicant: INSILICO MEDICINE IP LIMITED

Inventor： Aleksandrs Zavoronkovs ,  Yan Ivanenkov ,  Daniil Polykovskiy ,  Aleksandr Aliper

IPC: G16C20/50 ,  G16C20/70 ,  C07D487/04 ,  C07D231/56 ,  C07D403/10 ,  C07D471/10 ,  C12Q1/48 ,  G06N20/00 ,  G16H10/20

Abstract: A computer-implemented method can include: receiving input of a biological target; receiving a generative model (e.g., tensorial reinforcement learning (GENTRL) model or other model) trained with reference compounds, wherein the reference compounds include: general compounds, compounds that modulate the biological target, and compounds that modulate biomolecules other than the biological target; generating structures of generated compounds with the generative model; prioritizing structures of generated compounds based on at least one criteria; processing prioritized chemical structures of the generated compounds through a Sammon mapping protocol to obtain hit structures; and providing chemical structures of the hit structures. One or more non-transitory computer readable media are provided that store instructions that in response to being executed by one or more processors, cause a computer system to perform operations, the operations comprising performing the computer methods described herein for providing chemical structure of hit structures generated by the generative model.

公开(公告)号：US12227493B2

公开(公告)日：2025-02-18

申请号：US18348114

申请日：2023-07-06

Applicant: Insilico Medicine IP Limited

Inventor： Aleksandr Aliper ,  Vladimir Aladinskiy ,  Aleksandrs Zavoronkovs

IPC: C07D405/04 ,  A61K31/4164 ,  A61K31/4439 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04 ,  C07D491/048

Abstract: A method of inhibiting TNIK and/or MAP4K4 kinase can include: contacting the kinase with a compound of Formula A, wherein: ring 1 is an aromatic ring with or without hetero atoms; ring 2 is a hetero aromatic ring; ring 3 includes at least one hetero aromatic ring and optionally at least one cycloaliphatic ring fused with the at least one hetero aromatic ring; ring 4 is an aromatic ring with or without hetero atoms; Y is a bond or a linker; Y1 is a linker; each n is independently 0, 1, or 2; each o is independently 0. 1, 2, 3, 4, or 5; each R1, R6, R11, and R12 is independently a substituent; and RA is a ring structure, straight aliphatics, or branched aliphatics, which can be substituted or unsubstituted, any with or without hetero atoms.

公开(公告)号：US20240092765A1

公开(公告)日：2024-03-21

申请号：US18348114

申请日：2023-07-06

Applicant: Insilico Medicine IP Limited

Inventor： Aleksandr Aliper ,  Vladimir Aladinskiy ,  Aleksandrs Zavoronkovs

IPC: C07D405/04 ,  A61K31/4164 ,  A61K31/4439 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04 ,  C07D491/048

CPC classification number: C07D405/04 ,  A61K31/4164 ,  A61K31/4439 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04 ,  C07D491/048

Abstract: A method of inhibiting TNIK and/or MAP4K4 kinase can include: contacting the kinase with a compound of Formula A,






wherein: ring 1 is an aromatic ring with or without hetero atoms; ring 2 is a hetero aromatic ring; ring 3 includes at least one hetero aromatic ring and optionally at least one cycloaliphatic ring fused with the at least one hetero aromatic ring; ring 4 is an aromatic ring with or without hetero atoms; Y is a bond or a linker; Y1 is a linker; each n is independently 0, 1, or 2; each o is independently 0. 1, 2, 3, 4, or 5; each R1, R6, R11, and R12 is independently a substituent; and RA is a ring structure, straight aliphatics, or branched aliphatics, which can be substituted or unsubstituted, any with or without hetero atoms.

公开(公告)号：US20230115836A1

公开(公告)日：2023-04-13

申请号：US17817865

申请日：2022-08-05

Applicant: Insilico Medicine IP Limited

Inventor： Aleksandrs Zavoronkovs ,  Aleksandr Aliper ,  Vladimir Aladinskiy ,  Andrey Kukharenko

IPC: C07D403/04 ,  C07D233/90 ,  C07D403/14 ,  A61P13/12 ,  A61P11/00 ,  C07D487/08

Abstract: The disclosure provides TNIK and/or MAP4K4 kinases inhibitors for the treatment of disease. In one aspect, disclosed herein are kinase inhibitors having a structure of Formula (A), (A*), (I), (IIA), or (IIB). Further described herein are pharmaceutical composition comprising these compounds and methods of using these compounds. In one aspect, disclosed herein are methods of treating a disease or condition by administering the kinases inhibitors described herein.

公开(公告)号：US11530199B2

公开(公告)日：2022-12-20

申请号：US17678315

申请日：2022-02-23

Applicant: Insilico Medicine IP Limited

Inventor： Aleksandrs Zavoronkovs ,  Aleksandr Aliper ,  Vladimir Aladinskiy ,  Andrey Kukharenko

IPC: C07D403/06 ,  C07D403/14 ,  C07D233/90 ,  C07D401/04 ,  A61P11/00 ,  C07D405/04 ,  A61P13/12 ,  C07D487/08

Abstract: The disclosure provides TNIK and/or MAP4K4 kinases inhibitors for the treatment of disease. In one aspect, disclosed herein are kinase inhibitors having a structure of Formula (A), (A*), (I), (IIA), or (IIB). Further described herein are pharmaceutical composition comprising these compounds and methods of using these compounds. In one aspect, disclosed herein are methods of treating a disease or condition by administering the kinases inhibitors described herein.