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Integrated stress response pathway inhibitors

A compound, C1-C6 technology, used in applications, anti-inflammatory agents, biocides, etc., can solve problems such as increasing vegetable protein

Pending Publication Date: 2022-03-18
PRAXIS BIOTECH LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is a need to further increase the expression of plant proteins, which may require approaches other than genetic modification

Method used

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  • Integrated stress response pathway inhibitors
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0729] Embodiment 1. A compound of formula (I)

[0730]

[0731] or a pharmaceutically acceptable salt thereof,

[0732] in:

[0733] R I , R II , R III , R IV , R V , R VI , R VII and R VIII are independently selected from hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, -C(O)OH, -C(O)O(C 1 -C 6 Alkyl), -C(O)O(C 1 -C 6 haloalkyl), and halogen;

[0734] or, R I , R II , R III , R IV , R V , R VI , R VII and R VIII One of and R I , R II , R III , R IV , R V , R VI , R VII and R VIII the other together to form C 1 -C 6 Alkylene moiety;

[0735] or, selected from R I , R II , R III , R IV , R V , R VI , R VII and R VIII The two gem substituents together form an oxo group;

[0736] L A selected from

[0737] in# A Indicates the point of attachment to A and @ A Indicates a point of attachment to the rest of the molecule;

[0738] L B selected from

[0739] in# B Indicates the point of attachment to B and @ B Indicates a...

Embodiment approach 2

[0767] Embodiment 2. A compound of formula (A-1)

[0768]

[0769] or a pharmaceutically acceptable salt thereof, wherein:

[0770] R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are independently selected from hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, -C(O)OH, -C(O)O(C 1 -C 6 Alkyl), -C(O)O(C 1 -C 6 haloalkyl), and halogen;

[0771] or, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 One of and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 the other together to form C 1 -C 6 Alkylene moiety;

[0772] or, selected from R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 The two gem substituents together form an oxo group;

[0773] A 1 is the formula (A 1 Substituents of -1)

[0774]

[0775] where * indicates the point of attachment to the rest of the molecule;

[0776] W 1 selected from-C(R W1-1 R W1-2 )-, -N(R W1-2 )-, -C(R W1-1 R W1-1 )N(R W1-2 )-, -N(R W1-1 )C(R W1-1 R W1 -2 )-, -C(R W1-1 )=N-,-N=C(R W1-1...

Embodiment approach 3

[0789] Embodiment 3. A compound of formula (B-1)

[0790]

[0791] or a pharmaceutically acceptable salt thereof, wherein:

[0792] R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are independently selected from hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, -C(O)OH, -C(O)O(C 1 -C 6 Alkyl), -C(O)O(C 1 -C 6 haloalkyl), and halogen;

[0793] or, R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 One of and R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 the other together to form C 1 -C 6 Alkylene moiety;

[0794] or, selected from R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 The two gem substituents together form an oxo group;

[0795] R 17 is H, OH or NH 2 ;

[0796] A 3 is the formula (A 3 Substituents of -1)

[0797]

[0798] where * indicates the point of attachment to the rest of the molecule;

[0799] W 5 selected from-C(R W5-1 R W5-2 )-, -N(R W5-2 )-, -C(R W5-1 R W5-2 )N(R W5-2 )-, ...

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PUM

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Abstract

The present disclosure generally relates to therapeutic agents useful as inhibitors of the integrated stress response (ISR) pathway.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority to U.S. Provisional Patent Application Nos. 62 / 860,676, filed June 12, 2019, and 62 / 943,666, filed December 4, 2019, the disclosures of which are hereby incorporated by reference Incorporated into this article as a whole. technical field [0003] The present disclosure generally relates to therapeutic agents useful as inhibitors of the Integrative Stress Response (ISR) pathway. Background technique [0004] Genetic modification of plants to express heterologous proteins or to increase the expression of endogenous proteins has become an important tool for numerous businesses. Plants can be modified to express increased amounts of essential amino acids to achieve greater yields of the plants or proteins expressed therein, or to produce recombinant proteins such as biopolymers, industrial proteins / enzymes and therapeutic proteins. However, there is a need to further increa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/74C07D213/54C07D213/57
CPCC07D413/12C07D215/48C07D213/81C07D213/82C07D265/36C07D215/38C07D211/98C07D405/14C07D405/12C07D307/85C07D241/24C07D235/24C07D401/12C07D211/26C07D453/02C07C275/30C07C235/46C07C235/14C07C235/10A01P21/00A01N43/40A01N43/52A01N43/42A01N43/12A01N37/36A01N43/60A01N43/84A01N47/30A01N37/26C07D407/12A61K45/06C07D471/08A01N47/32C07D211/34C07D215/56C12P21/00C07C235/36A01N37/30A61K31/4709A61P25/00A61P29/00A61P35/00C07C235/34C07C237/20C07C235/42A01N47/10A01N43/08A01N47/28C07K16/00C07K14/485C12N15/81C07C2601/08
Inventor L·M·德尔加多·奥亚尔佐G·A·乌拉塔·迪亚兹B·普加拉D·潘帕蒂尔S·伯纳勒斯S·查克拉瓦蒂
Owner PRAXIS BIOTECH LLC