AR099991A1 - TGF-b INHIBITORS AND METHODS OF USE - Google Patents

TGF-b INHIBITORS AND METHODS OF USE

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Publication number
AR099991A1
AR099991A1 ARP150101066A ARP150101066A AR099991A1 AR 099991 A1 AR099991 A1 AR 099991A1 AR P150101066 A ARP150101066 A AR P150101066A AR P150101066 A ARP150101066 A AR P150101066A AR 099991 A1 AR099991 A1 AR 099991A1
Authority
AR
Argentina
Prior art keywords
alkyl
optionally substituted
halo
pyridinyl
phenyl
Prior art date
Application number
ARP150101066A
Other languages
Spanish (es)
Inventor
Kinsella Todd
Gelman Marina
Payan Donald
Ding Pingyu
Bhamidipati Somasekhar
Singh Rajinder
Original Assignee
Rigel Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Rigel Pharmaceuticals Inc filed Critical Rigel Pharmaceuticals Inc
Publication of AR099991A1 publication Critical patent/AR099991A1/en

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  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compuestos y un método de tratamiento de cáncer que comprende la administración a un sujeto que tiene cáncer de uno de los compuestos junto con otro tratamiento terapéutico del cáncer. Los compuestos inhiben la señalización por un miembro de la superfamilia de TGF-b (TGF: factor de crecimiento transformante) tales como Nodal o Activina. Reivindicación 1: Un compuesto, caracterizado porque tiene la fórmula (1), o una de sus sales farmacéuticamente aceptables, en donde Cy¹ es fenilo opcionalmente sustituido con 1, 2, 3 ó 4 restos seleccionados, de modo independiente, de halo; alquilo C₁₋₃ opcionalmente sustituido con 1, 2 ó 3 halo, etinilo o (trimetilsilil)etinilo; -O-alquilo C₁₋₃ opcionalmente sustituido con 1 - 3 halo; benzofuranilo; 2,3-dihidrobenzofuranilo; y feniletenilo; o, cuando hay un sustituyente simple en Cy¹, el sustituyente es uno de los anteriores sustituyentes del fenilo, -O-(alquil C₀₋₃)RIIIᵉ o - C(O)N(Rˣ)₂, en donde RIIIᵉ es fenilo, heteroarilo o heterocicloalquilo y cada Rˣ es, de modo independiente, H o alquilo C₁₋₃; Cy² es pirazolo[1,5-a]pirimidinilo; benzo[d]tiazolilo; imidazo[1,2-a]piridinilo opcionalmente sustituido con fenil-S(O)₂-; [1,2,4]triazolo[1,5-a]piridinilo; piridinilo; quinazolinilo; 1H-pirrolo[2,3-b]piridinilo; pirido[3,2-d]pirimidinilo opcionalmente sustituido con amino, metilamino o metoxi; o pirido[3,2-d]pirimidin-4(3H)-ona, en donde el quinazolinilo está opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados, de modo independiente, de -N(RIIIᵃ)₂; RIIIᵈ; alquilo C₁₋₃ opcionalmente sustituido con 1 - 3 halo; halo; metoxi; y -N(H)(alquil C₁₋₃)RIV; cada RIIIᵃ es, de modo independiente, H; alquilo C₁₋₆ opcionalmente sustituido con -C(O)OH, -C(O)O(alquilo C₁₋₃) o -CONH₂; o heteroarilo opcionalmente sustituido con alquilo C₁₋₃; RIIIᵈ es H o alquilo C₁₋₃ opcionalmente sustituido con 1 - 3 halo; RIV es H, alquilo C₁₋₃, -pirrolidonilo, 4-metilpiperzinilo, -N(alquil C₁₋₂)(alquilo C₁₋₂) o morfolinilo; y RIIIᶜ es H, halo, -OH, alquilo C₁₋₃ opcionalmente sustituido con 1 - 3 halo u -O-alquilo C₁₋₃ opcionalmente sustituido con 1 - 3 halo; siempre que el compuesto no sea uno de compuestos 1 - 974.Compounds and a method of cancer treatment comprising administration to a subject having cancer of one of the compounds together with another therapeutic treatment of cancer. The compounds inhibit signaling by a member of the TGF-b superfamily (TGF: transforming growth factor) such as Nodal or Activin. Claim 1: A compound, characterized in that it has the formula (1), or a pharmaceutically acceptable salt thereof, wherein Cy¹ is phenyl optionally substituted with 1, 2, 3 or 4 moieties selected, independently, from halo; C₁₋₃ alkyl optionally substituted with 1, 2 or 3 halo, ethynyl or (trimethylsilyl) ethynyl; -O-C₁₋₃ alkyl optionally substituted with 1-3 halo; benzofuranyl; 2,3-dihydrobenzofuranyl; and phenyletenyl; or, when there is a simple substituent on Cy¹, the substituent is one of the above phenyl substituents, -O- (C₀₋₃ alkyl) RIIIᵉ or -C (O) N (Rˣ) ₂, wherein RIIIᵉ is phenyl, heteroaryl or heterocycloalkyl and each Rˣ is, independently, H or C₁₋₃ alkyl; Cy² is pyrazolo [1,5-a] pyrimidinyl; benzo [d] thiazolyl; imidazo [1,2-a] pyridinyl optionally substituted with phenyl-S (O) ₂-; [1,2,4] triazolo [1,5-a] pyridinyl; pyridinyl; quinazolinyl; 1H-pyrrolo [2,3-b] pyridinyl; pyrido [3,2-d] pyrimidinyl optionally substituted with amino, methylamino or methoxy; or pyrido [3,2-d] pyrimidin-4 (3H) -one, wherein the quinazolinyl is optionally substituted with 1 or 2 substituents independently selected from -N (RIIIᵃ) ₂; RIIIᵈ; C₁₋₃ alkyl optionally substituted with 1-3 halo; halo; methoxy; and -N (H) (C₁₋₃ alkyl) RIV; each RIIIᵃ is, independently, H; C₁₋₆ alkyl optionally substituted with -C (O) OH, -C (O) O (C₁₋₃ alkyl) or -CONH₂; or heteroaryl optionally substituted with C₁₋₃ alkyl; RIIIᵈ is H or C₁₋₃ alkyl optionally substituted with 1-3 halo; RIV is H, C₁₋₃ alkyl, -pyrrolidonyl, 4-methylpiperzinyl, -N (C₁₋₂ alkyl) (C₁₋₂ alkyl) or morpholinyl; and RIIIᶜ is H, halo, -OH, C₁₋₃ alkyl optionally substituted with 1-3 halo or -O-C₁₋₃ alkyl optionally substituted with 1-3 halo; provided that the compound is not one of compounds 1-974.

ARP150101066A 2014-04-08 2015-04-08 TGF-b INHIBITORS AND METHODS OF USE AR099991A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201461976880P 2014-04-08 2014-04-08

Publications (1)

Publication Number Publication Date
AR099991A1 true AR099991A1 (en) 2016-08-31

Family

ID=58700003

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP150101066A AR099991A1 (en) 2014-04-08 2015-04-08 TGF-b INHIBITORS AND METHODS OF USE

Country Status (1)

Country Link
AR (1) AR099991A1 (en)

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