AR066147A1 - PIRAZOL-PIRIMIDINAS, PHARMACEUTICAL COMPOSITION, PROCESS AND USE IN MYELOPROLIFERATIVE DISORDERS, MYELODISPLASIC SYNDROME AND CANCER - Google Patents

PIRAZOL-PIRIMIDINAS, PHARMACEUTICAL COMPOSITION, PROCESS AND USE IN MYELOPROLIFERATIVE DISORDERS, MYELODISPLASIC SYNDROME AND CANCER

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AR066147A1
AR066147A1 ARP080101763A ARP080101763A AR066147A1 AR 066147 A1 AR066147 A1 AR 066147A1 AR P080101763 A ARP080101763 A AR P080101763A AR P080101763 A ARP080101763 A AR P080101763A AR 066147 A1 AR066147 A1 AR 066147A1
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Argentina
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heterocyclyl
carbocyclyl
alkyl
case
alkynyl
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ARP080101763A
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Spanish (es)
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Huiping Guan
Jeffrey Johannes
Bin Yang
Barry Raymond Hayter
Michelle Lamb
Bo Peng
Stephanos Ioannidis
Shan Huang
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Astrazeneca Ab
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Publication of AR066147A1 publication Critical patent/AR066147A1/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Reivindicacion 1: Un compuesto caracterizado porque responde a la formula (1) o una sal aceptable para uso farmacéutico del mismo, en donde: el anillo A se selecciona entre fenilo y heterociclilo de 6 miembros, en donde dichos fenilo y heterociclilo de 5 o 6 miembros están opcionalmente sustituidos con uno o más R5; X se selecciona entre -NH-, -O-, y -S-; R1 se selecciona entre H, -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo de 3 a 5 miembros, heterociclilo de 5 miembros, -OR1a, - SR1a, -N(R1a)2, -N(R1a)C(O)R1b, N(R1a)N(R1a)2, -NO2, -C(O)H, -C(O)R1b, -C(O)2R1a, -C(O)N(R1a)2, -OC(O)N(R1a)2, -N(R1a)C(O)2R1a, -N(R1a)C(O)N(R1a)2, -OC(O)R1b, -S(O)R1b, S(O)2R1b, -S(O)2N(R1a)2, -N(R1a)S(O)2R1b, -C(R1a)=N(R1a), y C(R1a)=N(OR1a), en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo de 3 a 5 miembros y heterociclilo de 5 miembros están opcionalmente sustituidos con uno o más R10; R1a en cada caso se selecciona en forma independiente entre H, alquilo C1-6, carbociclilo de 3 a 5 miembros, y heterociclilo de 5 miembros, en donde dichos alquilo C1-6, carbociclilo de 3 a 5 miembros, y heterociclilo de 5 miembros en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R10; R1b en cada caso se selecciona en forma independiente entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo de 3 a 5 miembros, y heterociclilo de 5 miembros, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo de 3 a 5 miembros, y heterociclilo de 5 miembros, en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R10; R2 en cada caso se selecciona en forma independiente entre halo, -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, heterociclilo, -OR2a, -SR2a, N(R2a)2, N(R2a)c(o)R2b, N(R2a)N(R2a)2, -NO2, -C(O)H, -C(O)R2b, -C(O)2R2a, -C(O)N(R2a)2, -OC(O)N(R2a)2, -N(R2a)C(O)2R2a, -N(R2a)C(O)N(R2a)2, -OC(O)R2b, -S(O)R2b, -S(O)2R2b, -S(O)2N(R2a)2, -N(R2a)S(O)2R2b, -C(R2a)=N(R2a), y -C(R2a)=N(OR2a), en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo están opcionalmente sustituidos con uno o más R20; R2a en cada caso se selecciona en forma independiente entre H, alquilo C1-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R20; R2b en cada caso se selecciona en forma independiente entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R20; R3 se selecciona entre H, halo, -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, heterociclilo, -OR3a, -SR3a, -N(R3a)2, -N(R3a)C(O)R3b, -N(R3a)N(R3a)2, -NO2, -C(O)H, C(O)R3b, -C(O)2R3a, -c(o)N(R3a)2, -OC(O)N(R3a)2, -N(R3a)c(o)2R3a, -N(R3a)C(O)N(R3a)2, -OC(O)R3b, -S(O)R3b, -S(O)2R3b, -s(o)2N(R3a)2, -N(R3a)S(O)2R3b, -C(R3a)=N(R3a), y -C(R3a)=N(OR3a), en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo están opcionalmente sustituidos con uno o más R30; R3a en cada caso se selecciona en forma independiente entre H, alquilo C1-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R30; R3b en cada caso se selecciona en forma independiente entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6,, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R30; R4 se selecciona entre -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, heterociclilo, -N(R4a)C(O)R4b, N(R4a)N(R4a)2, -NO2, -C(O)H, -C(O)R4b, -C(O)2R4a, -c(o)N(R4a)2, -OC(O)N(R4a)2, -N(R4a)C(O)2R4a, -N(R4a)C(O)N(R4a)2, -OC(O)R4b, -S(O)R4b, -S(O)2R4b, -S(O)2N(R4a)2, -N(R4a)S(O)2R4b, C(R4a)=N(R4a), y -C(R4a)=N(OR4a), en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo están opcionalmente sustituidos con uno o más R40; R4a en cada caso se selecciona en forma independiente entre H, alquilo C1-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R40; R4b en cada caso se selecciona en forma independiente entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R40; R5 en cada caso se selecciona en forma independiente entre halo, -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, heterociclilo, -OR5a, -SR5a, -N(R5a)2, -N(R5a)C(O)R5b, -N(R5a)N(R5a)2, -NO2, -C(O)H, -C(O)R5b, -C(O)2R5a, -C(O)N(R5a)2, -OC(O)N(R5a)2, -N(R5a)C(O)2R5a, -N(R5a)c(o)N(R5a)2, -OC(O)R5b, -S(O)R5b, -S(O)2R5b, -S(O)2N(R5a)2, -N(R5a)S(O)2R5b, -C(R5a)=N(R5a), y -C(R5a)=N(OR5a), en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso están opcionalmente sustituidos con uno o más R50; R5a en cada caso se selecciona en forma independiente entre H, alquilo C1-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R50; R5b en cada caso se selecciona en forma independiente entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más R50; R10 en cada caso se selecciona en forma independiente entre halo, -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, heterociclilo, -OR10a, -SR10a, -N(R10a)2, -N(R10a)C(O)R10b, -N(R10a)N(R10a)2, -NO2, -C(O)H, -C(O)R10b, -c(o)2R10a, -c(o)N(R10a)2, -OC(O)N(R10a)2, -N(R10a)C(O)2R10a, -N(R10a)C(O)N(R10a)2, -OC(O)R10b, -S(O)R10b, -S(O)2R10b, -S(O)2N(R10a)2, -N(R10a)S(O)2R10b, -C(R10a)=N(R10a), y -C(R10a)=N(OR10a), en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Ra; R10a en cada caso se selecciona en forma independiente entre H, alquilo C1-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Ra; R10b en cada caso se selecciona en forma independiente entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Ra; R20 en cada caso se selecciona en forma independiente entre halo, -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, heterociclilo, -OR20a, -SR20a, -N(R20a)2, -N(R20a)C(O)R20b, -N(R20a)N(R20a)2, -NO2, -C(O)H, -C(O)R20b, -C(O)2R20a, -C(O)N(R20a)2, -OC(O)N(R20a)2, -N(R20a)C(O)2R20a, -N(R20a)C(O)N(R20a)2, -OC(O)R20b, -S(O)R20b, -S(O)2R20b, -S(O)2N(R2a)2, -N(R20a)S(O)2R20b, -C(R20a)=N(R20a), y -C(R20a)=N(OR20a), en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Rb; R20a en cada caso se selecciona en forma independiente entre H, alquilo C1-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Rb; R20b en cada caso se selecciona en forma independiente entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Rb; R30 en cada caso se selecciona en forma independiente entre halo, -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, heterociclilo, -OR30a, -SR30a, -N(R30a)2, -N(R30a)C(O)R30b, -N(R30a)N(R30a)2, -NO2, -C(O)H, -C(O)R30b, -C(O)2R30a, -C(O)N(R30a)2, -OC(O)N(R30a)2, -N(R30a)c(o)2R30a, -N(R30a)c(o)N(R30a)2, -OC(O)R30b, -S(O)R30b, -S(O)2R30b, -S(O)2N(R30a)2, -N(R30a)S(O)2R30b, -C(R30a)=N(R30a), y C(R30a)=N(OR30a), en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Rc; R30a en cada caso se selecciona en forma independiente entre H, alquilo C1-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Rc; R30b en cada caso se selecciona en forma independiente entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo, en donde dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, y heterociclilo en cada caso y en forma independiente están opcionalmente sustituidos con uno o más Rc; R40 en cada caso se selecciona en forma independiente entre halo, -CN, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, carbociclilo, heterociclilo, -OR40a, SR40a, -N(R40a)2, -N(R40a)c(o)R40b, -N(R40a)N(R40a)2, -NO2, -C(O)H, -C(O)R40b, -C(O)2R40a, -c(o)N(R40a)2, -OC(O)N(R40a)2, -N(R40a)c(o)2R40a, N(R40a)C(O)N(R40a)2, -OC(O)R40b, -S(O)R40b, -S(O)2R40b, -S(O)2N(R40a)2, -N(R40a)S(O)2R40b, -C(R40a)=N(R40a), y -C(R40a)=N(OR40a), en donde dichos alClaim 1: A compound characterized in that it responds to formula (1) or a salt acceptable for pharmaceutical use thereof, wherein: ring A is selected from 6-membered phenyl and heterocyclyl, wherein said 5 or 6 phenyl and heterocyclyl members are optionally substituted with one or more R5; X is selected from -NH-, -O-, and -S-; R1 is selected from H, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 3 to 5 membered carbocyclyl, 5 membered heterocyclyl, -OR1a, - SR1a, -N (R1a) 2, - N (R1a) C (O) R1b, N (R1a) N (R1a) 2, -NO2, -C (O) H, -C (O) R1b, -C (O) 2R1a, -C (O) N (R1a) 2, -OC (O) N (R1a) 2, -N (R1a) C (O) 2R1a, -N (R1a) C (O) N (R1a) 2, -OC (O) R1b, - S (O) R1b, S (O) 2R1b, -S (O) 2N (R1a) 2, -N (R1a) S (O) 2R1b, -C (R1a) = N (R1a), and C (R1a) = N (OR1a), wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 3 to 5 membered carbocyclyl and 5 member heterocyclyl are optionally substituted with one or more R10; R1a in each case is independently selected from H, C1-6 alkyl, 3 to 5 member carbocyclyl, and 5 member heterocyclyl, wherein said C1-6 alkyl, 3 to 5 member carbocyclyl, and 5 member heterocyclyl in each case and independently they are optionally substituted with one or more R10; R1b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 3 to 5 membered carbocyclyl, and 5 membered heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl , C2-6 alkynyl, 3 to 5 membered carbocyclyl, and 5 membered heterocyclyl, in each case and independently are optionally substituted with one or more R10; R2 in each case is independently selected from halo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, heterocyclyl, -OR2a, -SR2a, N (R2a) 2, N (R2a) c (o) R2b, N (R2a) N (R2a) 2, -NO2, -C (O) H, -C (O) R2b, -C (O) 2R2a, -C (O) N (R2a) 2 , -OC (O) N (R2a) 2, -N (R2a) C (O) 2R2a, -N (R2a) C (O) N (R2a) 2, -OC (O) R2b, -S (O) R2b, -S (O) 2R2b, -S (O) 2N (R2a) 2, -N (R2a) S (O) 2R2b, -C (R2a) = N (R2a), and -C (R2a) = N (OR2a), wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R20; R2a in each case is independently selected from H, C1-6 alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more R20; R2b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more R20; R3 is selected from H, halo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, heterocyclyl, -OR3a, -SR3a, -N (R3a) 2, -N (R3a) C ( O) R3b, -N (R3a) N (R3a) 2, -NO2, -C (O) H, C (O) R3b, -C (O) 2R3a, -c (o) N (R3a) 2, - OC (O) N (R3a) 2, -N (R3a) c (o) 2R3a, -N (R3a) C (O) N (R3a) 2, -OC (O) R3b, -S (O) R3b, -S (O) 2R3b, -s (o) 2N (R3a) 2, -N (R3a) S (O) 2R3b, -C (R3a) = N (R3a), and -C (R3a) = N (OR3a ), wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl optionally are substituted with one or more R30; R3a in each case is independently selected from H, C1-6 alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more R30; R3b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl , and heterocyclyl in each case and independently are optionally substituted with one or more R30; R4 is selected from -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, heterocyclyl, -N (R4a) C (O) R4b, N (R4a) N (R4a) 2, -NO2, -C (O) H, -C (O) R4b, -C (O) 2R4a, -c (o) N (R4a) 2, -OC (O) N (R4a) 2, -N (R4a) C ( O) 2R4a, -N (R4a) C (O) N (R4a) 2, -OC (O) R4b, -S (O) R4b, -S (O) 2R4b, -S (O) 2N (R4a) 2 , -N (R4a) S (O) 2R4b, C (R4a) = N (R4a), and -C (R4a) = N (OR4a), wherein said C1-6 alkyl, C2-6 alkenyl, C2- alkynyl 6, carbocyclyl, and heterocyclyl are optionally substituted with one or more R40; R4a in each case is independently selected from H, C1-6 alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more R40; R4b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more R40; R5 in each case is independently selected from halo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, heterocyclyl, -OR5a, -SR5a, -N (R5a) 2, -N ( R5a) C (O) R5b, -N (R5a) N (R5a) 2, -NO2, -C (O) H, -C (O) R5b, -C (O) 2R5a, -C (O) N ( R5a) 2, -OC (O) N (R5a) 2, -N (R5a) C (O) 2R5a, -N (R5a) c (o) N (R5a) 2, -OC (O) R5b, -S (O) R5b, -S (O) 2R5b, -S (O) 2N (R5a) 2, -N (R5a) S (O) 2R5b, -C (R5a) = N (R5a), and -C (R5a ) = N (OR5a), wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case are optionally substituted with one or more R50; R5a in each case is independently selected from H, C1-6 alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more R50; R5b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more R50; R10 in each case is independently selected from halo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, heterocyclyl, -OR10a, -SR10a, -N (R10a) 2, -N ( R10a) C (O) R10b, -N (R10a) N (R10a) 2, -NO2, -C (O) H, -C (O) R10b, -c (o) 2R10a, -c (o) N ( R10a) 2, -OC (O) N (R10a) 2, -N (R10a) C (O) 2R10a, -N (R10a) C (O) N (R10a) 2, -OC (O) R10b, -S (O) R10b, -S (O) 2R10b, -S (O) 2N (R10a) 2, -N (R10a) S (O) 2R10b, -C (R10a) = N (R10a), and -C (R10a ) = N (OR10a), wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Ra; R10a in each case is independently selected from H, C1-6 alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Ra; R10b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Ra; R20 in each case is independently selected from halo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, heterocyclyl, -OR20a, -SR20a, -N (R20a) 2, -N ( R20a) C (O) R20b, -N (R20a) N (R20a) 2, -NO2, -C (O) H, -C (O) R20b, -C (O) 2R20a, -C (O) N ( R20a) 2, -OC (O) N (R20a) 2, -N (R20a) C (O) 2R20a, -N (R20a) C (O) N (R20a) 2, -OC (O) R20b, -S (O) R20b, -S (O) 2R20b, -S (O) 2N (R2a) 2, -N (R20a) S (O) 2R20b, -C (R20a) = N (R20a), and -C (R20a ) = N (OR20a), wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Rb; R20a in each case is independently selected from H, C1-6 alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Rb; R20b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Rb; R30 in each case is independently selected from halo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, heterocyclyl, -OR30a, -SR30a, -N (R30a) 2, -N ( R30a) C (O) R30b, -N (R30a) N (R30a) 2, -NO2, -C (O) H, -C (O) R30b, -C (O) 2R30a, -C (O) N ( R30a) 2, -OC (O) N (R30a) 2, -N (R30a) c (o) 2R30a, -N (R30a) c (o) N (R30a) 2, -OC (O) R30b, -S (O) R30b, -S (O) 2R30b, -S (O) 2N (R30a) 2, -N (R30a) S (O) 2R30b, -C (R30a) = N (R30a), and C (R30a) = N (OR30a), wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Rc; R30a in each case is independently selected from H, C1-6 alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Rc; R30b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl in each case and independently are optionally substituted with one or more Rc; R40 in each case is independently selected from halo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, heterocyclyl, -OR40a, SR40a, -N (R40a) 2, -N (R40a ) c (o) R40b, -N (R40a) N (R40a) 2, -NO2, -C (O) H, -C (O) R40b, -C (O) 2R40a, -c (o) N (R40a ) 2, -OC (O) N (R40a) 2, -N (R40a) c (o) 2R40a, N (R40a) C (O) N (R40a) 2, -OC (O) R40b, -S (O ) R40b, -S (O) 2R40b, -S (O) 2N (R40a) 2, -N (R40a) S (O) 2R40b, -C (R40a) = N (R40a), and -C (R40a) = N (OR40a), where said at

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