AR120905A1

AR120905A1 - DERIVATIVES OF [1,2,4]TRIAZOLO[4,3-A]QUINAZOLINE AS MODULATORS OF DIACYLGLYCEROL-KINASE

Info

Publication number: AR120905A1
Application number: ARP200103651A
Authority: AR
Inventors: Masaaki Sawa; Mai Arai; Ryoko Nakai; Hirokazu Matsumoto; Catherine Pugh; Eric Hu; Juan Guerrero; Jesse Jacobsen; Jonathan William Medley; Jie Xu; Latesh Lad; Leena Patel; Michael Graupe; Qingming Zhu; Stephen Holmbo; Tetsuya Kobayashi; Will Watkins; Yasamin Moazami; Suet C Yeung; Julian A Codelli
Original assignee: Carna Biosciences Inc; Gilead Sciences Inc
Priority date: 2019-12-24
Filing date: 2020-12-23
Publication date: 2022-03-30

Abstract

Compuestos derivados de [1,2,4]triazolo[4,3-a]quinazolina como inhibidores de DGKa, composiciones farmacéuticas que los comprenden y su uso para el tratamiento de una infección por VIH o el virus de la Hepatitis B como así también para tratar diversos tipos de cáncer, diferentes clases de leucemia y la inhibición de la metástasis. Reivindicación 1: Un compuesto de fórmula (1) o una sal farmacéuticamente aceptable del mismo, en el que R¹ es hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, alcoxi C₁₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆ o CN; R² es hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -NO, -NO₂, -C(O)R²ᵃ, -C(O)OR²ᵃ, -OC(O)R²ᵃ, -C(O)N(R²ᵃ)(R²ᵇ), -N(R²ᵃ)C(O)R²ᵇ, -OC(O)N(R²ᵃ)(R²ᵇ), -N(R²ᵃ)C(O)OR²ᵇ, -C(=NR²ᵃ)N(R²ᵇ)(R²ᶜ), -N(R²ᵃ)(R²ᵇ), -N(R²ᵃ)N(R²ᵇ)(R²ᶜ), -N(R²ᵃ)N=C(R²ᵇ)(OR²ᶜ), -OR²ᵃ, -SR²ᵃ, -S(O)R²ᵃ, -S(O)(NR²ᵃ)(R²ᵇ), -S(NR²ᵃ)(NR²ᵇ)(R²ᶜ), -S(O)₂R²ᵃ, -S(O)₂N(R²ᵃ)(R²ᵇ), -N(R²ᵃ)S(O)₂(R²ᵇ), -P(R²ᵃ)(R²ᵇ), -P(O)(R²ᵃ)(R²ᵇ), -P(O)(OR²ᵃ)(R²ᵇ), -P(O)(OR²ᵃ)(OR²ᵇ), cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo), en donde cada alquilo, alquenilo o alquinilo está independientemente sustituido opcionalmente con 1 a 3 R²ᵈ grupos, cada cicloalquilo está opcionalmente sustituido con 1 a 3 R²ᵉ grupos, cada arilo está opcionalmente sustituido con 1 a 3 R²ᶠ grupos, cada heterocicloalquilo está opcionalmente sustituido con 1 a 3 R²ᵍ grupos y cada heteroarilo está opcionalmente sustituido con 1 a 3 R²ʰ grupos; cada R²ᵃ, R²ᵇ y R²ᶜ es independientemente hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo), en donde el arilo o heteroarilo está opcionalmente sustituido con 1 a 3 R²ʲ; alternativamente, R²ᵃ, R²ᵇ y R²ᶜ cuando están unidos al mismo átomo se pueden combinar con el átomo al que están unidos para formar un alquilo heterocíclico; cada R²ᵈ es independientemente -CN, -C(O)R²ᵈ¹, -C(O)OR²ᵈ¹, -OC(O)R²ᵈ¹, -C(O)N(R²ᵈ¹)(R²ᵈ²), -N(R²ᵈ¹)C(O)R²ᵈ², -OC(O)N(R²ᵈ¹)(R²ᵈ²), -N(R²ᵈ¹)C(O)OR²ᵈ², -N(R²ᵈ¹)(R²ᵈ²), =O, -OR²ᵈ¹, -SR²ᵈ¹, -S(O)R²ᵈ¹, -S(O)(NR²ᵈ¹)(R²ᵈ²), -S(O)₂R²ᵈ¹, -S(O)N(R²ᵈ¹)(R²ᵈ²), -N(R²ᵈ¹)S(O)₂R²ᵈ², cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo); cada R²ᵈ¹ y R²ᵈ² es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆ o haloalquilo C₁₋₆; cada R²ᵉ, R²ᶠ, R²ᵍ y R²ʰ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN o -OH; cada R²ʲ es independientemente alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆ o haloalcoxi C₁₋₆; R³ es hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -NO, -NO₂, -C(O)R³ᵃ, -C(O)OR³ᵃ, -OC(O)R³ᵃ, -C(O)N(R³ᵃ)(R³ᵇ), -N(R³ᵃ)C(O)R³ᵇ, -OC(O)N(R³ᵃ)(R³ᵇ), -N(R³ᵃ)C(O)OR³ᵇ, -C(=NR³ᵃ)N(R³ᵇ)(R³ᶜ), -N(R³ᵃ)(R³ᵇ), -N(R³ᵃ)N(R³ᵇ)(R³ᶜ), -N(R³ᵃ)N=C(R³ᵇ)(OR³ᶜ), -OR³ᵃ, -SR³ᵃ, -S(O)R³ᵃ, -S(O)(NR³ᵃ)(R³ᵇ), -S(NR³ᵃ)(NR³ᵇ)(R³ᶜ), -S(O)₂R³ᵃ, -S(O)₂N(R³ᵃ)(R³ᵇ), -N(R³ᵃ)S(O)₂(R³ᵇ), -P(R³ᵃ)(R³ᵇ), -P(O)(R³ᵃ)(R³ᵇ), -P(O)(OR³ᵃ)(R³ᵇ), -P(O)(OR³ᵃ)(OR³ᵇ), cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo), en donde cada alquenilo o alquinilo está independientemente sustituido opcionalmente con 1 a 3 R³ᵈ grupos, cada cicloalquilo está opcionalmente sustituido con 1 a 3 R³ᵉ grupos, cada arilo está opcionalmente sustituido con 1 a 3 R³ᶠ grupos, cada heterocicloalquilo está opcionalmente sustituido con 1 a 3 R³ᵍ grupos y cada heteroarilo está opcionalmente sustituido con 1 a 3 R³ʰ grupos; cada R³ᵃ, R³ᵇ y R³ᶜ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo o heteroarilo; alternativamente, R³ᵃ, R³ᵇ y R³ᶜ cuando están unidos al mismo átomo se pueden combinar con el átomo al que están unidos para formar un heterocicloalquilo; cada R³ᵈ es independientemente -N(R³ᵈ¹)(R³ᵈ²), -OR³ᵈ¹, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo o heteroarilo; cada R³ᵈ¹ y R³ᵈ² es independientemente hidrógeno, alquilo C₁₋₆ o -C(O)O-(alquilo C₁₋₆); cada R³ᵉ, R³ᶠ, R³ᵍ y R³ʰ es independientemente hidrógeno, alquilo C₁₋₆, alcoxi C₁₋₆, halógeno, haloalquilo C₁₋₆ o haloalcoxi C₁₋₆; R⁴ es hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, alcoxi C₁₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆ o -CN; R⁵ es hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo), en donde el alquilo está opcionalmente sustituido con R⁵ᵃ; R⁵ᵃ es -OSi(R⁵ᵃ¹)(R⁵ᵃ²)(R⁵ᵃ³); R⁵ᵃ¹, R⁵ᵃ² y R⁵ᵃ³ son cada uno independientemente alquilo C₁₋₆; y R⁶ es alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, arilo C₆₋₁₂ o heteroarilo, en donde el arilo o heteroarilo están cada uno opcionalmente sustituido con 1 a 3 R⁶ᵃ; cada R⁶ᵃ es independientemente alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -NO₂, -C(O)R⁶ᵇ, -C(O)OR⁶ᵇ, -OC(O)R⁶ᵇ, -C(O)N(R⁶ᵇ)(R⁶ᶜ), -N(R⁶ᵇ)C(O)R⁶ᶜ, -C(=NR⁶ᵇ)N(R⁶ᶜ)(R⁶ᵈ), -N(R⁶ᵇ)(R⁶ᶜ), -OR⁶ᵇ, -SR⁶ᵇ, -S(O)R⁶ᵇ, -S(O)₂R⁶ᵇ, -S(NR⁶ᵇ)(NR⁶ᶜ)R⁶ᵈ, -S(O)(NR⁶ᵇ)(R⁶ᶜ), -S(O)₂N(R⁶ᵇ)(R⁶ᶜ), -N(R⁶ᵇ)S(O)₂(R⁶ᶜ), -P(R⁶ᵇ)(R⁶ᶜ), -P(O)(R⁶ᵇ)(R⁶ᶜ), -P(O)(OR⁶ᵇ)(R⁶ᶜ), -P(O)(OR⁶ᵇ)(OR⁶ᶜ), cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo), en donde el cicloalquilo, arilo, heterocicloalquilo o heteroarilo está cada uno opcionalmente sustituido con 1 a 3 R⁶ᵉ, el alquilo está opcionalmente sustituido con R⁶ᶠ y el alquinilo está opcionalmente sustituido con 1 a 4 R⁶ʲ; cada R⁶ᵇ, R⁶ᶜ y R⁶ᵈ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo), en donde el cicloalquilo, arilo, heterocicloalquilo o heteroarilo está opcionalmente sustituido por 1 a 3 R⁶ᵏ; cada R⁶ᵏ es independientemente alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, heterocicloalquilo o alquilo C₁₋₆-(heterocicloalquilo); cada R⁶ᵉ es independientemente alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -NO₂, -C(O)R⁶ᵉ¹, -C(O)OR⁶ᵉ¹, -OC(O)R⁶ᵉ¹, -C(O)N(R⁶ᵉ¹)(R⁶ᵉ²), -N(R⁶ᵉ¹)C(O)R⁶ᵉ², -OC(O)N(R⁶ᵉ¹)(R⁶ᵉ²), -N(R⁶ᵉ¹)C(O)OR⁶ᵉ², -C(=NR⁶ᵉ¹)N(R⁶ᵉ²)(R⁶ᵉ³), -N(R⁶ᵉ¹)(R⁶ᵉ²), =O, -OR⁶ᵉ¹, -SR⁶ᵉ¹, -S(O)R⁶ᵉ¹, -S(NR⁶ᵉ¹)(NR⁶ᵉ²), -S(O)(NR⁶ᵉ¹)(R⁶ᵉ²), -S(O)₂R⁶ᵉ¹, -S(O)₂N(R⁶ᵉ¹)(R⁶ᵉ²), -SF₅, -N(R⁶ᵉ¹)S(O)₂(R⁶ᵉ²), -P(R⁶ᵉ¹)(R⁶ᵉ²), -P(O)(R⁶ᵉ¹)(R⁶ᵉ²), -P(O)(OR⁶ᵉ¹)(R⁶ᵉ²), -P(O)(OR⁶ᵉ¹)(OR⁶ᵉ²), -Si(R⁶ᵉ¹)(R⁶ᵉ²)(R⁶ᵉ³), cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, alquilo C₁₋₆-arilo C₆₋₁₂, heterocicloalquilo, alquilo C₁₋₆-heterocicloalquilo, heteroarilo o alquilo C₁₋₆-heteroarilo, en donde el cicloalquilo, arilo, heterocicloalquilo o heteroarilo está cada uno opcionalmente sustituido con 1 a 3 R⁶ʰ y el alquilo está opcionalmente sustituido con 1 a 3 R⁶ᵐ; cada R⁶ᵉ¹, R⁶ᵉ² y R⁶ᵉ³ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₁₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₀, alquilo C₁₋₆-arilo C₆₋₁₀, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo), en donde el cicloalquilo, arilo, heterocicloalquilo o heteroarilo está opcionalmente sustituido con 1 a 3 R⁶ⁿ; cada R⁶ⁿ es alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -C(O)R⁶ⁿ¹, -C(O)OR⁶ⁿ¹, -OC(O)R⁶ⁿ¹, -C(O)N(R⁶ⁿ¹)(R⁶ⁿ²), -N(R⁶ⁿ¹)C(O)R⁶ⁿ², -OC(O)N(R⁶ⁿ¹)(R⁶ⁿ²), -N(R⁶ⁿ¹)C(O)OR⁶ⁿ², -C(=NR⁶ⁿ¹)N(R⁶ⁿ²)(R⁶ⁿ³), -N(R⁶ⁿ¹)(R⁶ⁿ²), =O, -OH, -SR⁶ⁿ¹, -S(O)R⁶ⁿ¹, -S(NR⁶ⁿ¹)(NR⁶ⁿ²)R⁶ⁿ³, -S(O)(NR⁶ⁿ¹)(R⁶ⁿ²), -S(O)₂R⁶ⁿ¹, -S(O)₂N(R⁶ⁿ¹)(R⁶ⁿ²) o -N(R⁶ⁿ¹)S(O)₂(R⁶ⁿ²); cada R⁶ⁿ¹, R⁶ⁿ² y R⁶ⁿ³ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₀, alquilo C₁₋₆-arilo C₆₋₁₀, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo); cada R⁶ʰ es independientemente alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -C(O)R⁶ʰ¹, -C(O)OR⁶ʰ¹, -OC(O)R⁶ʰ¹, -C(O)N(R⁶ʰ¹)(R⁶ʰ²), -N(R⁶ʰ¹)C(O)R⁶ʰ², -OC(O)N(R⁶ʰ¹)(R⁶ʰ²), -N(R⁶ʰ¹)C(O)OR⁶ʰ², -C(=NR⁶ʰ¹)N(R⁶ʰ²)(R⁶ʰ³), -N(R⁶ʰ¹)(R⁶ʰ²), =O, -OH, -SR⁶ʰ¹, -S(O)R⁶ʰ¹, -S(NR⁶ʰ¹)(NR⁶ʰ²)R⁶ʰ³, -S(O)(NR⁶ʰ¹)(R⁶ʰ²), -S(O)₂R⁶ʰ¹, -S(O)₂N(R⁶ʰ¹)(R⁶ʰ²), -N(R⁶ʰ¹)S(O)₂(R⁶ʰ²), cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, heterocicloalquilo o alquilo C₁₋₆-(heterocicloalquilo); cada R⁶ʰ¹, R⁶ʰ² y R⁶ʰ³ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₀, alquilo C₁₋₆-arilo C₆₋₁₀, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo); cada R⁶ᵐ es independientemente halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -C(O)R⁶ᵐ¹, -C(O)OR⁶ᵐ¹, -OC(O)R⁶ᵐ¹, -C(O)N(R⁶ᵐ¹)(R⁶ᵐ²), -N(R⁶ᵐ³)C(O)R⁶ᵐ², -OC(O)N(R⁶ᵐ¹)(R⁶ᵐ²), -N(R⁶ᵐ¹)C(O)OR⁶ᵐ², -C(=NR⁶ᵐ³)N(R⁶ᵐ¹)(R⁶ᵐ²), -N(R⁶ᵐ¹)(R⁶ᵐ²), =O, -OH, -SR⁶ᵐ¹, -S(O)R⁶ᵐ¹, -S(NR⁶ᵐ¹)(NR⁶ᵐ²)R⁶ᵐ³, -S(O)(NR⁶ᵐ¹)(R⁶ᵐ²), -S(O)₂R⁶ᵐ¹, -S(O)₂N(R⁶ᵐ¹)(R⁶ᵐ²) o -N(R⁶ᵐ³)S(O)₂(R⁶ᵐ²); cada R⁶ᵐ¹, R⁶ᵐ² y R⁶ᵐ³ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₀, alquilo C₁₋₆-arilo C₆₋₁₀, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo); R⁶ᶠ es -OSi(R⁶ᶠ¹)(R⁶ᶠ²)(R⁶ᶠ³); R⁶ᶠ¹, R⁶ᶠ² y R⁶ᶠ³ son cada uno independientemente alquilo C₁₋₆; cada R⁶ʲ es independientemente alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -C(O)R⁶ʲ¹, -C(O)OR⁶ʲ¹, -OC(O)R⁶ʲ¹, -C(O)N(R⁶ʲ¹)(R⁶ʲ²), -N(R⁶ʲ³)C(O)R⁶ʲ², -OC(O)N(R⁶ʲ¹)(R⁶ʲ²), -N(R⁶ʲ¹)C(O)OR⁶ʲ², -C(=NR⁶ʲ³)N(R⁶ʲ¹)(R⁶ʲ²), -N(R⁶ʲ¹)(R⁶ʲ²), =O, -OR⁶ʲ¹, -SR⁶ʲ¹, -S(O)R⁶ʲ¹, -S(NR⁶ʲ¹)(NR⁶ʲ²), -S(NR⁶ʲ¹)(NR⁶ʲ²)R⁶ʲ³, -S(O)(NR⁶ʲ¹)(R⁶ʲ²), -S(O)₂R⁶ʲ¹, -S(O)₂N(R⁶ʲ¹)(R⁶ʲ²), -N(R⁶ʲ¹)S(O)₂(R⁶ʲ²), -Si(R⁶ʲ¹)(R⁶ʲ²)(R⁶ʲ³), cicloalquilo C₃₋₁₀, arilo C₆₋₁₂, heterocicloalquilo o heteroarilo, en donde el cicloalquilo, arilo, heterocicloalquilo o heteroarilo está opcionalmente sustituido con 1 a 3 R⁶ᵖ; cada R⁶ʲ¹, R⁶ʲ² y R⁶ʲ³ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₀, alquilo C₁₋₆-arilo C₆₋₁₀, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo); cada R⁶ᵖ es independientemente alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆, -CN, -C(O)R⁶ᵖ¹, -C(O)OR⁶ᵖ¹, -OC(O)R⁶ᵖ¹, -C(O)N(R⁶ᵖ¹)(R⁶ᵖ²), -N(R⁶ᵖ¹)C(O)R⁶ᵖ², -OC(O)N(R⁶ᵖ¹)(R⁶ᵖ²), -N(R⁶ᵖ¹)C(O)OR⁶ᵖ², -C(=NR⁶ᵖ³)N(R⁶ᵖ¹)(R⁶ᵖ²), -N(R⁶ᵖ¹)(R⁶ᵖ²), =O, -OH, -SR⁶ᵖ¹, -S(O)R⁶ᵖ¹, -S(NR⁶ᵖ¹)(NR⁶ᵖ²)R⁶ᵖ³, -S(O)(NR⁶ᵖ¹)(R⁶ᵖ²), -S(O)₂R⁶ᵖ¹, -S(O)₂N(R⁶ᵖ¹)(R⁶ᵖ²) o -N(R⁶ᵖ¹)S(O)₂(R⁶ᵖ²); cada R⁶ᵖ¹, R⁶ᵖ² y R⁶ᵖ³ es independientemente hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, arilo C₆₋₁₀, alquilo C₁₋₆-arilo C₆₋₁₀, heterocicloalquilo, alquilo C₁₋₆-(heterocicloalquilo), heteroarilo o alquilo C₁₋₆-(heteroarilo); o R⁵ y un R⁶ᵃ junto con los átomos a los que están unidos forman un heterocicloalquilo opcionalmente sustituido con 1 a 3 R⁶ᵍ; cada R⁶ᵍ es independientemente alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxialquilo C₂₋₆, halógeno, haloalquilo C₁₋₆, haloalcoxi C₁₋₆ o -CN; R⁷ es hidrógeno, alquilo C₁₋₆, hidroxialquilo C₁₋₆, aminoalquilo C₁₋₆, alcoxi C₁₋₆, alcoxialquilo C₂₋₆, alquiltio C₁₋₆, halógeno, haloalquilo C₁₋₆, -CN, -OH, -NH₂, cicloalquilo C₃₋₁₀, alquilo C₁₋₆-cicloalquilo C₃₋₁₀, heterocicloalquilo o alquilo C₁₋₆-(heterocicloalquilo); cada heterocicloalquilo es un anillo de 3 a 20 miembros que tienen 1 a 4 heteroátomos cada uno independientemente N, O ó S; y cada heteroarilo es un anillo de 5 a 18 miembros que tienen 1 a 4 heteroátomos cada uno independientemente N, O ó S; proporcionado que R⁵ y R⁶ no son ambos alquilo C₁₋₄; y cuando R⁵ es hidrógeno, R⁶ no es isopropilo o fenilo sustituido con 2-Me. Compounds derived from [1,2,4]triazolo[4,3-a]quinazoline as DGKa inhibitors, pharmaceutical compositions that comprise them and their use for the treatment of HIV or Hepatitis B virus infection as well as to treat various types of cancer, different classes of leukemia and the inhibition of metastasis. Claim 1: A compound of formula (1) or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, halogen, C₁₋ haloalkyl ₆, C₁₋₆ haloalkoxy or CN; R² is hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₋ haloalkyl, C₆₋ haloalkoxy , -CN, -NO, -NO₂, -C(O)R²ᵃ, -C(O)OR²ᵃ, -OC(O)R²ᵃ, -C(O)N(R²ᵃ)(R²ᵇ), -N(R²ᵃ)C (O)R²ᵇ, -OC(O)N(R²ᵃ)(R²ᵇ), -N(R²ᵃ)C(O)OR²ᵇ, -C(=NR²ᵃ)N(R²ᵇ)(R²ᶜ), -N(R²ᵃ)(R²ᵇ ), -N(R²ᵃ)N(R²ᵇ)(R²ᶜ), -N(R²ᵃ)N=C(R²ᵇ)(OR²ᶜ), -OR²ᵃ, -SR²ᵃ, -S(O)R²ᵃ, -S(O)(NR²ᵃ )(R²ᵇ), -S(NR²ᵃ)(NR²ᵇ)(R²ᶜ), -S(O)₂R²ᵃ, -S(O)₂N(R²ᵃ)(R²ᵇ), -N(R²ᵃ)S(O)₂(R²ᵇ) , -P(R²ᵃ)(R²ᵇ), -P(O)(R²ᵃ)(R²ᵇ), -P(O)(OR²ᵃ)(R²ᵇ), -P(O)(OR²ᵃ)(OR²ᵇ), C₃₋₁₀ cycloalkyl , C₁₋₆-alkyl-C₃₋₁₀-cycloalkyl, C₆₋₁₂-aryl, C₁₋₆-alkyl-C₆₋₁₂-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl), where each alkyl, alkenyl, or alkynyl is independently optionally substituted with 1 to 3 R²ᵈ groups, each cycloalkyl is optionally substituted with 1 to 3 R²ᵉ groups, each aryl is optionally substituted with 1 to 3 R²ᶠ groups, each heterocycloalkyl is optionally substituted with 1 to 3 R²ᵍ groups and each heteroaryl is optionally substituted with 1 to 3 R²ʰ groups; each R²ᵃ, R²ᵇ and R²ᶜ is independently hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋ cycloalkyl C₁₋₆-alkyl-C₃₋₁₀-cycloalkyl, C₆₋₁₂-aryl, C₁₋₆-alkyl-C₆₋₁₂-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl), wherein the aryl or heteroaryl is optionally substituted with 1 to 3 R²ʲ; alternatively, R²ᵃ, R²ᵇ and R²ᶜ when attached to the same atom may combine with the atom to which they are attached to form a heterocyclic alkyl; each R²ᵈ is independently -CN, -C(O)R²ᵈ¹, -C(O)OR²ᵈ¹, -OC(O)R²ᵈ¹, -C(O)N(R²ᵈ¹)(R²ᵈ²), -N(R²ᵈ¹)C(O) R²ᵈ², -OC(O)N(R²ᵈ¹)(R²ᵈ²), -N(R²ᵈ¹)C(O)OR²ᵈ², -N(R²ᵈ¹)(R²ᵈ²), =O, -OR²ᵈ¹, -SR²ᵈ¹, -S(O)R²ᵈ¹ , -S(O)(NR²ᵈ¹)(R²ᵈ²), -S(O)₂R²ᵈ¹, -S(O)N(R²ᵈ¹)(R²ᵈ²), -N(R²ᵈ¹)S(O)₂R²ᵈ², C₃₋₁₀ cycloalkyl, alkyl C₁₋₆-C₃₋₁₀-cycloalkyl, C₆₋₁₂-aryl, C₁₋₆-alkyl-C₆₋₁₂-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl); each R²ᵈ¹ and R²ᵈ² is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl or C₁₋₆ haloalkyl; each R²ᵉ, R²ᶠ, R²ᵍ and R²ʰ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₆ haloalkyl, C₋₋ haloalkoxy, - CN or -OH; each R²ʲ is independently C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₆ haloalkyl, or C₁₋₆ haloalkoxy; R³ is hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₋ haloalkyl, C₆₋ haloalkoxy , -CN, -NO, -NO₂, -C(O)R³ᵃ, -C(O)OR³ᵃ, -OC(O)R³ᵃ, -C(O)N(R³ᵃ)(R³ᵇ), -N(R³ᵃ)C (O)R³ᵇ, -OC(O)N(R³ᵃ)(R³ᵇ), -N(R³ᵃ)C(O)OR³ᵇ, -C(=NR³ᵃ)N(R³ᵇ)(R³ᶜ), -N(R³ᵃ)(R³ᵇ ), -N(R³ᵃ)N(R³ᵇ)(R³ᶜ), -N(R³ᵃ)N=C(R³ᵇ)(OR³ᶜ), -OR³ᵃ, -SR³ᵃ, -S(O)R³ᵃ, -S(O)(NR³ᵃ )(R³ᵇ), -S(NR³ᵃ)(NR³ᵇ)(R³ᶜ), -S(O)₂R³ᵃ, -S(O)₂N(R³ᵃ)(R³ᵇ), -N(R³ᵃ)S(O)₂(R³ᵇ) , -P(R³ᵃ)(R³ᵇ), -P(O)(R³ᵃ)(R³ᵇ), -P(O)(OR³ᵃ)(R³ᵇ), -P(O)(OR³ᵃ)(OR³ᵇ), C₃₋₁₀ cycloalkyl , C₁₋₆-alkyl-C₃₋₁₀-cycloalkyl, C₆₋₁₂-aryl, C₁₋₆-alkyl-C₆₋₁₂-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl), where each alkenyl or alkynyl is independently optionally substituted with 1 to 3 R³ᵈ groups, each cycloalkyl is optionally substituted with 1 to 3 R³ᵉ groups, each aryl is optionally substituted with 1 to 3 R³ᶠ groups, each heteroci chloroalkyl is optionally substituted with 1 to 3 R³ᵍ groups and each heteroaryl is optionally substituted with 1 to 3 R³ʰ groups; each R³ᵃ, R³ᵇ and R³ᶜ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋₁₀ cycloalkyl, C₁₋₆ alkyl-C₃₋₋-C₀cycloalkyl, aryl C₁₋₆alkyl-C₆₋₁₂aryl, heterocycloalkyl or heteroaryl; alternatively, R³ᵃ, R³ᵇ and R³ᶜ when attached to the same atom may combine with the atom to which they are attached to form a heterocycloalkyl; each R³ᵈ is independently -N(R³ᵈ¹)(R³ᵈ²), -OR³ᵈ¹, C₃₋₁₀ cycloalkyl, C₁₋₆ alkyl-C₃₋₁₀ cycloalkyl, C₆₋₁₂ aryl, C₁₋₆ alkyl-C₆₋₁₂aryl, heteroaryl, or cycloalkyl each R³ᵈ¹ and R³ᵈ² is independently hydrogen, C₁₋₆ alkyl or -C(O)O-(C₁₋₆ alkyl); each R³ᵉ, R³ᶠ, R³ᵍ and R³ʰ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, halogen, C₁₋₆ haloalkyl or C₁₋₆ haloalkoxy; R⁴ is hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, halogen, C₁₋₆ haloalkyl, C₁₋₆ haloalkoxy, or -CN; R⁵ is hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋₁₀ cycloalkyl, C₁₋₋₆ alkyl, C₁₁₋ cycloalkyl C₆₋₁₂, C₁₋₆-alkyl-C₆₋₁₂-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl), wherein the alkyl is optionally substituted with R⁵ᵃ; R⁵ᵃ is -OSi(R⁵ᵃ¹)(R⁵ᵃ²)(R⁵ᵃ³); R⁵ᵃ¹, R⁵ᵃ² and R⁵ᵃ³ are each independently C₁₋₆ alkyl; and R⁶ is C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ haloalkyl, C₆₋₁₂ aryl, or heteroaryl, wherein aryl or heteroaryl is each optionally substituted with 1 to 3 R⁶ᵃ; each R⁶ᵃ is independently C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₋ haloalkyl, C₋₋ haloalkyl, , -CN, -NO₂, -C(O)R⁶ᵇ, -C(O)OR⁶ᵇ, -OC(O)R⁶ᵇ, -C(O)N(R⁶ᵇ)(R⁶ᶜ), -N(R⁶ᵇ)C(O) R⁶ᶜ, -C(=NR⁶ᵇ)N(R⁶ᶜ)(R⁶ᵈ), -N(R⁶ᵇ)(R⁶ᶜ), -OR⁶ᵇ, -SR⁶ᵇ, -S(O)R⁶ᵇ, -S(O)₂R⁶ᵇ, -S(NR⁶ᵇ) (NR⁶ᶜ)R⁶ᵈ, -S(O)(NR⁶ᵇ)(R⁶ᶜ), -S(O)₂N(R⁶ᵇ)(R⁶ᶜ), -N(R⁶ᵇ)S(O)₂(R⁶ᶜ), -P(R⁶ᵇ)( R⁶ᶜ), -P(O)(R⁶ᵇ)(R⁶ᶜ), -P(O)(OR⁶ᵇ)(R⁶ᶜ), -P(O)(OR⁶ᵇ)(OR⁶ᶜ), C₃₋₁₀-cycloalkyl, C₁₋₆-cycloalkyl C₃₋₁₀, C₆₋₁₂ aryl, C₁₋₆ alkyl-C₆₋₁₂ aryl, heterocycloalkyl, C₁₋₆ alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆ alkyl-(heteroaryl), wherein cycloalkyl, aryl, heterocycloalkyl or heteroaryl is each optionally substituted with 1 to 3 R⁶ᵉ, alkyl is optionally substituted with R⁶ᶠ and alkynyl is optionally substituted with 1 to 4 R⁶ʲ; each R⁶ᵇ, R⁶ᶜ and R⁶ᵈ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋₁₀ cycloalkyl, C₁₋₆-cycloalkyl C₆₋₁₂-aryl, C₁₋₆-alkyl-C₆₋₁₂-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl), wherein cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted by 1 to 3 R⁶ᵏ; each R⁶ᵏ is independently C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkoxy, C₃₋₋₁₀ cycloalkyl, cycloalkyl C₃₋₁₀, heterocycloalkyl or C₁₋₆ alkyl-(heterocycloalkyl); each R⁶ᵉ is independently C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₋ haloalkyl, C₋₋ haloalkyl, , -CN, -NO₂, -C(O)R⁶ᵉ¹, -C(O)OR⁶ᵉ¹, -OC(O)R⁶ᵉ¹, -C(O)N(R⁶ᵉ¹)(R⁶ᵉ²), -N(R⁶ᵉ¹)C(O) R⁶ᵉ², -OC(O)N(R⁶ᵉ¹)(R⁶ᵉ²), -N(R⁶ᵉ¹)C(O)OR⁶ᵉ², -C(=NR⁶ᵉ¹)N(R⁶ᵉ²)(R⁶ᵉ³), -N(R⁶ᵉ¹)(R⁶ᵉ²), = O, -OR⁶ᵉ¹, -SR⁶ᵉ¹, -S(O)R⁶ᵉ¹, -S(NR⁶ᵉ¹)(NR⁶ᵉ²), -S(O)(NR⁶ᵉ¹)(R⁶ᵉ²), -S(O)₂R⁶ᵉ¹, -S(O)₂N( R⁶ᵉ¹)(R⁶ᵉ²), -SF₅, -N(R⁶ᵉ¹)S(O)₂(R⁶ᵉ²), -P(R⁶ᵉ¹)(R⁶ᵉ²), -P(O)(R⁶ᵉ¹)(R⁶ᵉ²), -P(O)( OR⁶ᵉ¹)(R⁶ᵉ²), -P(O)(OR⁶ᵉ¹)(OR⁶ᵉ²), -Si(R⁶ᵉ¹)(R⁶ᵉ²)(R⁶ᵉ³), C₃₋₁₀-cycloalkyl, C₁₋₆-alkyl-C₃₋₁₀-cycloalkyl, C₁₋-aryl,₆₋ C₁₋₆ alkyl-C₆₋₁₂ aryl, heterocycloalkyl, C₁₋₆ alkyl-heterocycloalkyl, heteroaryl, or C₁₋₆ alkyl-heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl or heteroaryl is each optionally substituted with 1 to 3 R⁶ʰ and the alkyl is optionally substituted with 1 to 3 R⁶ᵐ; each R⁶ᵉ¹, R⁶ᵉ² and R⁶ᵉ³ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋₁₀ cycloalkyl, C₀₋-cycloalkyl C₆₋₁₀-aryl, C₁₋₆-alkyl-C₆₋₁₀-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl), wherein cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with 1 to 3 R⁶ⁿ; each R⁶ⁿ is C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₋haloalkyl, C₋₋cohaloal -CN, -C(O)R⁶ⁿ¹, -C(O)OR⁶ⁿ¹, -OC(O)R⁶ⁿ¹, -C(O)N(R⁶ⁿ¹)(R⁶ⁿ²), -N(R⁶ⁿ¹)C(O)R⁶ⁿ², -OC (O)N(R⁶ⁿ¹)(R⁶ⁿ²), -N(R⁶ⁿ¹)C(O)OR⁶ⁿ², -C(=NR⁶ⁿ¹)N(R⁶ⁿ²)(R⁶ⁿ³), -N(R⁶ⁿ¹)(R⁶ⁿ²), =O, -OH , -SR⁶ⁿ¹, -S(O)R⁶ⁿ¹, -S(NR⁶ⁿ¹)(NR⁶ⁿ²)R⁶ⁿ³, -S(O)(NR⁶ⁿ¹)(R⁶ⁿ²), -S(O)₂R⁶ⁿ¹, -S(O)₂N(R⁶ⁿ¹)( R⁶ⁿ²) or -N(R⁶ⁿ¹)S(O)₂(R⁶ⁿ²); each R⁶ⁿ¹, R⁶ⁿ² and R⁶ⁿ³ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋₁₁₀ cycloalkyl, C₀₋-cycloalkyl C₆₋₁₀-aryl, C₁₋₆-alkyl-C₆₋₁₀-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl); each R⁶ʰ is independently C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₆₆ haloalkyl, C₁₋₆ haloalkyl, , -CN, -C(O)R⁶ʰ¹, -C(O)OR⁶ʰ¹, -OC(O)R⁶ʰ¹, -C(O)N(R⁶ʰ¹)(R⁶ʰ²), -N(R⁶ʰ¹)C(O)R⁶ʰ², - OC(O)N(R⁶ʰ¹)(R⁶ʰ²), -N(R⁶ʰ¹)C(O)OR⁶ʰ², -C(=NR⁶ʰ¹)N(R⁶ʰ²)(R⁶ʰ³), -N(R⁶ʰ¹)(R⁶ʰ²), =O, - OH, -SR⁶ʰ¹, -S(O)R⁶ʰ¹, -S(NR⁶ʰ¹)(NR⁶ʰ²)R⁶ʰ³, -S(O)(NR⁶ʰ¹)(R⁶ʰ²), -S(O)₂R⁶ʰ¹, -S(O)₂N(R⁶ʰ¹) (R⁶ʰ²), -N(R⁶ʰ¹)S(O)₂(R⁶ʰ²), C₃₋₁₀-cycloalkyl, C₁₋₆-alkyl-C₃₋₁₀-cycloalkyl, heterocycloalkyl or C₁₋₆-alkyl-(heterocycloalkyl); each R⁶ʰ¹, R⁶ʰ² and R⁶ʰ³ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋₁₀ cycloalkyl, C₁₋₆ cycloalkyl, C₁₋₆ alkyl C₆₋₁₀-aryl, C₁₋₆-alkyl-C₆₋₁₀-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl); each R⁶ᵐ is independently halogen, C₁₋₆ haloalkyl, C₁₋₆ haloalkoxy, -CN, -C(O)R⁶ᵐ¹, -C(O)OR⁶ᵐ¹, -OC(O)R⁶ᵐ¹, -C(O)N(R⁶ᵐ¹)( R⁶ᵐ²), -N(R⁶ᵐ³)C(O)R⁶ᵐ², -OC(O)N(R⁶ᵐ¹)(R⁶ᵐ²), -N(R⁶ᵐ¹)C(O)OR⁶ᵐ², -C(=NR⁶ᵐ³)N(R⁶ᵐ¹)(R⁶ᵐ² ), -N(R⁶ᵐ¹)(R⁶ᵐ²), =O, -OH, -SR⁶ᵐ¹, -S(O)R⁶ᵐ¹, -S(NR⁶ᵐ¹)(NR⁶ᵐ²)R⁶ᵐ³, -S(O)(NR⁶ᵐ¹)(R⁶ᵐ²), - S(O)₂R⁶ᵐ¹, -S(O)₂N(R⁶ᵐ¹)(R⁶ᵐ²) or -N(R⁶ᵐ³)S(O)₂(R⁶ᵐ²); each R⁶ᵐ¹, R⁶ᵐ², and R⁶ᵐ³ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, cycloalkyl, C₁₋₋ alkyl, C₁₆-C₃₋ cycloalkyl ₁₀, C₁₋₆-alkyl-C₆₋₁₀-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl); R⁶ᶠ is -OSi(R⁶ᶠ¹)(R⁶ᶠ²)(R⁶ᶠ³); R⁶ᶠ¹, R⁶ᶠ² and R⁶ᶠ³ are each independently C₁₋₆ alkyl; each R⁶ʲ is independently C₂₋₆ alkoxyalkyl, halogen, C₁₋₆ haloalkyl, C₁₋₆ haloalkoxy, -CN, -C(O)R⁶ʲ¹, -C(O)OR⁶ʲ¹, -OC(O)R⁶ʲ¹, -C(O) N(R⁶ʲ¹)(R⁶ʲ²), -N(R⁶ʲ³)C(O)R⁶ʲ², -OC(O)N(R⁶ʲ¹)(R⁶ʲ²), -N(R⁶ʲ¹)C(O)OR⁶ʲ², -C(=NR⁶ʲ³)N (R⁶ʲ¹)(R⁶ʲ²), -N(R⁶ʲ¹)(R⁶ʲ²), =O, -OR⁶ʲ¹, -SR⁶ʲ¹, -S(O)R⁶ʲ¹, -S(NR⁶ʲ¹)(NR⁶ʲ²), -S(NR⁶ʲ¹)(NR⁶ʲ²)R⁶ʲ³ , -S(O)(NR⁶ʲ¹)(R⁶ʲ²), -S(O)₂R⁶ʲ¹, -S(O)₂N(R⁶ʲ¹)(R⁶ʲ²), -N(R⁶ʲ¹)S(O)₂(R⁶ʲ²), -Si( R⁶ʲ¹)(R⁶ʲ²)(R⁶ʲ³), C₃₋₁₀ cycloalkyl, C₆₋₁₂ aryl, heterocycloalkyl or heteroaryl, wherein cycloalkyl, aryl, heterocycloalkyl or heteroaryl is optionally substituted with 1 to 3 R⁶ᵖ; each R⁶ʲ¹, R⁶ʲ², and R⁶ʲ³ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋₁₀ cycloalkyl, C₁₋₆ cycloalkyl, C₁₋₆ alkyl C₆₋₁₀-aryl, C₁₋₆-alkyl-C₆₋₁₀-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl); each R⁶ᵖ is independently C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, halogen, C₁₋₆ haloalkyl, C₁₋₆ haloalkoxy, -CN, -CᵖR¶ , -C(O)OR⁶ᵖ¹, -OC(O)R⁶ᵖ¹, -C(O)N(R⁶ᵖ¹)(R⁶ᵖ²), -N(R⁶ᵖ¹)C(O)R⁶ᵖ², -OC(O)N(R⁶ᵖ¹)(R⁶ᵖ² ), -N(R⁶ᵖ¹)C(O)OR⁶ᵖ², -C(=NR⁶ᵖ³)N(R⁶ᵖ¹)(R⁶ᵖ²), -N(R⁶ᵖ¹)(R⁶ᵖ²), =O, -OH, -SR⁶ᵖ¹, -S(O) R⁶ᵖ¹, -S(NR⁶ᵖ¹)(NR⁶ᵖ²)R⁶ᵖ³, -S(O)(NR⁶ᵖ¹)(R⁶ᵖ²), -S(O)₂R⁶ᵖ¹, -S(O)₂N(R⁶ᵖ¹)(R⁶ᵖ²) or -N(R⁶ᵖ¹)S (O)₂(R⁶ᵖ²); each R⁶ᵖ¹, R⁶ᵖ², and R⁶ᵖ³ is independently hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl, C₁₋₆ haloalkyl, C₃₋₁₀ cycloalkyl, C₀₋-cycloalkyl C₆₋₁₀-aryl, C₁₋₆-alkyl-C₆₋₁₀-aryl, heterocycloalkyl, C₁₋₆-alkyl-(heterocycloalkyl), heteroaryl, or C₁₋₆-alkyl-(heteroaryl); or R⁵ and one R⁶ᵃ together with the atoms to which they are attached form a heterocycloalkyl optionally substituted with 1 to 3 R⁶ᵍ; each R⁶ᵍ is independently C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₂₋₆ alkoxyalkyl, halogen, C₁₋₆ haloalkyl, C₁₋ haloalkoxy, or -₆; R⁷ is hydrogen, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ aminoalkyl, C₁₋₆ alkoxy, C₂₋₆ alkoxyalkyl, C₁₋₆ alkylthio, halogen, C₁₋₆ haloalkyl, -CN, -OH, -NH₂, C₃₋₁₀ cycloalkyl, C₁₋₆ alkyl-C₃₋₁₀ cycloalkyl, heterocycloalkyl or C₁₋₆ alkyl-(heterocycloalkyl); each heterocycloalkyl is a 3 to 20 membered ring having 1 to 4 heteroatoms each independently N, O or S; and each heteroaryl is a 5 to 18 membered ring having 1 to 4 heteroatoms each independently N, O or S; provided that R⁵ and R⁶ are not both C₁₋₄ alkyl; and when R⁵ is hydrogen, R⁶ is not isopropyl or phenyl substituted with 2-Me.