AR066910A1 - Antagonistas de receptor de urotensina ii - Google Patents

Antagonistas de receptor de urotensina ii

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Publication number
AR066910A1
AR066910A1 ARP080102425A ARP080102425A AR066910A1 AR 066910 A1 AR066910 A1 AR 066910A1 AR P080102425 A ARP080102425 A AR P080102425A AR P080102425 A ARP080102425 A AR P080102425A AR 066910 A1 AR066910 A1 AR 066910A1
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Argentina
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alkyl
amino
alkoxy
heteroaryl
sulfonyl
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ARP080102425A
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Janssen Pharmaceutica Nv
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Publication of AR066910A1 publication Critical patent/AR066910A1/es

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    • C07D401/12—Heterocyclic 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 two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
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    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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Abstract

Uso como antagonistas del receptor de urotensina II, y composiciones farmacéuticas. Reivindicacion 1: Un compuesto de la formula (1) en el cual, A es un enlace o se selecciona entre el grupo integrado por a-1, a-2 opcionalmente insaturado, a-3, a-4, a-5 opcionalmente insaturado y a-6 opcionalmente insaturado, en el cual, la porcion inferior de A está unida, con respecto al átomo de nitrogeno de la formula (1), a la posicion 3 o 4 en la porcion de anillo de benceno de la formula (1) en el cual, cuando A está presente, entonces G es hidrogeno, o un sustituyente seleccionado entre alquilo C1-8, alquenilo C2-8, cicloalquilo C3-14 o una porcion -C[(R1)(R11)]-L-D, resto de formula (3), o dos sustituyentes alquilo C1-4, ambos unidos al átomo de nitrogeno comun del anillo de la formula (1), formando de ese modo una sal de amonio cuaternario; R1 se selecciona entre el grupo integrado por hidrogeno, alquilo C1-8, alquenilo C2-8, y alquinilo C2-8; R11 se selecciona entre el grupo integrado por hidrogeno, alquilo C1-8 y ciclopropilo; L está ausente o es alquilo C1-4; D es arilo, cicloalquilo C3-14, cicloalquenilo C5-14, heterociclilo, o heteroarilo, en el cual arilo y heteroarilo es sustituido de manera opcional con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre el grupo integrado por alquilo C1-3, alcoxi C1-3, alquenilo C2-8, alqueniloxi C2-3, hidroxi, alquiltio C1-3, fluor, cloro, ciano, alquilcarbonilo C1-3, (alquilcarbonil C1-3)amino, (alquil C1-3)amino, di(alquil C1-3)amino y cicloalquilo C2-14, en el cual cicloalquilo C3-14 es sustituido de manera opcional con uno, dos, tres o cuatro sustituyentes alquilo C1-3; R4 es hidrogeno o alquilo C1-8; L2 es -C(R2)(R5)-(CR6R7)r-, en el cual r es 0, 1 o 2; y en el cual R5, R6, y R7 son en forma independiente hidrogeno o alquilo C1-3; R2 se selecciona entre el grupo integrado por heteroarilo, fenilo, heterociclilo y alquilo C1-6, en el cual fenilo es sustituido de manera opcional con [(R200-aIquil C1-6)(Ra)]amino, [(R200-sulfonil)(Ra)]amino o [(hidroxisulfonil)(Ra)]amino, en el cual heterociclilo es sustituido de manera opcional con alquilo C1-4, arilo, heteroarilo, R200-alquilo C1-6 o R200-sulfonilo, y en el cual alquilo C1-6 es sustituido de manera opcional con carboxi, hidroxi, R200, NRaRb, alcoxi C1-6, R200-alcoxi C1-6, R200-oxi, R200-tio, aminocarbonilo, carboxi-alcoxi C1-6, aminocarbonil-alcoxi C1-6, (alquil C1-6)aminocarbonilo, di(alquil C1-6)aminocarbonilo, [(R200-alquil C1-6)(Ra)]amino, (R200-aIquil C1-6)2-amino, (alquil C1-6-carbonil)amino, (trihalo-alquil C1-4-carbonil)amino, (R200-alquil C1-6-carbonil)amino, (alcoxi C1-6-carbonil)amino, (R200-alcoxi C1-6-carbonil)amino, (alcoxi C1-6-alquil C1-6-carbonil)amino, (R200-carbonil)amino, (amino-alquil C1-6-carbonil)amino, [(alquil C1-6)amino-alquil C1-4-carbonil]amino, [di(alquil C1-6)amino-alquil C1-6)amino-alquil C1-6-carbonil]amino, (alquil C1-6-carbonil-acetonitrilo-carbonil)amino, ureido, tioureido, acetamidino, guanidino, ({[(R200)(Ra)]aminocarbonil}(Ra))amino, [(R200-oxicarbonil)(Ra)]amino, [(R200)(Ra)]aminocarboniloxi, aminosulfonilo, alquil C1-6sulfonilo, hidroxisulfonilo, (alquil C1-6sulfonil)amino, (R200-alquil C1-6-sulfonil)amino, (R200-alquenil C2-6-sulfonil)amino, (alquil C1-6-sulfonil-alquil C1-6sulfonil)amino, R200-sulfoniloxi, aminosulfoniloxi, (alquil C1-6)aminosulfoniloxi, di(alquil C1-6)aminosulfoniloxi, [(aminosulfonil)(Ra)]amino, {[(alquil C1-6)aminosulfonil](Ra)}amino, {[di(alquil C1-6)aminosulfonil](Ra)}amino, [(hidroxisulfonil)(Ra)]amino, [(R200-oxisulfonil)(Ra)]amino, [(R200-sulfonil)(Ra)]amino, [(R200)(Ra)]aminosulfoniloxi, o ({[(R200)(Ra)]aminosulfonil}(Rc))amino; Ra se selecciona entre el grupo integrado por hidrogeno, alquilo C1-6, alquil C1-6carbonil y cicloalquilo C3-8; Rb se selecciona entre el grupo integrado por hidrogeno, alquilo C1-6 o R201, R200 es arilo C6-10, heteroarilo, cicloalquilo C3-8 o heterociclilo, cada uno sustituido de manera opcional con uno, dos o tres sustituyentes seleccionados en forma independiente entre el grupo integrado por alquilo C1-4, trihalo-alquilo C1-4, alcoxi C1-4, trihalo-alcoxi C1-4, alquil C1-6-carbonilo, alcoxi C1-6-carbonilo, amino, alquil C1-6-amino, dialquil C1-6-amino, (alquil C1-6-carbonil)amino, alquil C1-6-sulfonilo, hidroxisulfonilo, aminosulfonilo, cloro, fluor, bromo y R202, en el cual cicloalquilo C3-8 o heterociclilo es sustituido de manera opcional con uno, dos o tres sustituyentes oxo sobre elementos disponibles del anillo de átomos de carbono en el cual heteroarilo que tiene un elemento de anillo de átomos de nitrogeno es sustituido de manera opcional en el átomo de nitrogeno del anillo con un sustituyente oxi formando de ese modo un oxido; R201, es arilo C6-10, heteroarilo, cicloalquilo C3-8 o heterociclilo, en el cual arilo, heteroarilo, cicloalquilo C3-8 o heterociclilo están cada uno sustituido de manera opcional con uno, dos o tres sustituyentes seleccionados en forma independiente entre el grupo integrado por alquilo C1-4, trihalo-alquilo C1-4, alcoxi C1-4, trihalo-alcoxi C1-4, amino, alquil C1-6-amino, dialquil C1-6-amino, alquil C1-6-carbonilo, alcoxi C1-6-carbonilo, (alquil C1-6-carbonil)amino, alquil C1-6-sulfonilo, hidroxisulfonilo, aminosulfonilo, cloro, fluor, bromo, arilo, heteroarilo, aril-alquil C1-6, aril-sulfonilo y heteroaril-sulfonilo, en el cual cicloalquilo C3-8 o heterociclilo es sustituido de manera opcional con uno, dos o tres sustituyentes oxo sobre elementos disponibles del anillo de átomos de carbono en el cual heteroarilo que tiene un elemento de anillo de átomos de nitrogeno es sustituido de manera opcional en el átomo de nitrogeno del anillo con un sustituyente oxi formando de ese modo un oxido; R202 es arilo, heteroarilo, aril-alquilo C1-6, [(aril-alquil C1-6)(Ra)]amino, hidroxisulfonilo, aril-sulfonilo, heteroaril-sulfonilo o [(heteroaril-sulfonil)(Ra)]amino, en el cual cada arilo y heteroarilo es sustituido de manera opcional con uno, dos o tres sustituyentes alquilo C1-4; B es arilo C6-10, tetralinilo, indanilo, o un heteroarilo seleccionado entre el grupo integrado por piridin-2-ilo, piridin-4-ilo, pirazol-4-ilo, pirimidin-4-ilo, pirimidin-5-ilo, pirazin-2-ilo, imidazol-1-ilo, tien-2-ilo, isoquinolinilo, indolilo, quinolinilo, y tiazol-5-ilo, en el cual B es sustituido de manera opcional con uno, dos o tres sustituyentes seleccionados en forma independiente entre el grupo integrado por alquilo C1-4, alcoxi C1-4, alcoxi C1-4 fluorado, halogeno, ciano, hidroxi, aminocarbonilo, alquil C1-4-aminocarbonilo, dialquil C1-4-aminocarbonilo, aminosulfonilo, alquil C1-4-aminosulfonilo, dialquil C1-4-aminosulfonilo, hidroxisulfonilo, aminosulfonilamino, alquil C1-4-aminosulfonilamino, dialquil C1-4-aminosulfonilamino, aminosulfoniloxi, alquil C1-4-aminosulfoniloxi, y dialquil C1-4-aminosulfoniloxi, siempre que cuando B se selecciona entre el grupo integrado por arilo C6-10, tetralinilo, indanilo, tien-2-ilo, e indolilo, entonces B es sustituido en forma independiente con dos a tres sustituyentes seleccionados entre el grupo integrado por alcoxi C1-3 y hidroxi, siempre que, cuando B es fenilo sustituido en las posiciones 3,4-, 3,5- o 4,5- con un sustituyente alcoxi C1-3 no ramificado en cada posicion, entonces fenilo puede ser adicionalmente sustituido en forma opcional en una posicion 3-, 4-, o 5- abierta restante con un alcoxi C1-3 adicional o un sustituyente hidroxi; E es hidrogeno, halogeno, ciano, alquilo C1-3, alcoxi C1-3, alquenilo C2-5, amino, alquil C1-3-amino o di-alquil C1-3-amino; X es O u S y enantiomeros, diastereomeros, tautomeros, solvatos, y sales aceptables para uso farmacéutico.
ARP080102425A 2007-06-07 2008-06-06 Antagonistas de receptor de urotensina ii AR066910A1 (es)

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US (2) US8008299B2 (es)
EP (1) EP2161994A4 (es)
JP (1) JP5466154B2 (es)
KR (1) KR20100031604A (es)
CN (1) CN101677548A (es)
AR (1) AR066910A1 (es)
AU (1) AU2008262360B2 (es)
BR (1) BRPI0812773A2 (es)
CA (1) CA2690080A1 (es)
CL (1) CL2008001672A1 (es)
IL (1) IL202454A0 (es)
PA (1) PA8782701A1 (es)
TW (1) TW200911256A (es)
UY (1) UY31121A1 (es)
WO (1) WO2008153902A2 (es)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2659412A1 (en) 2006-07-31 2008-02-07 Janssen Pharmaceutica N.V. Urotensin ii receptor antagonists
PA8782701A1 (es) 2007-06-07 2009-01-23 Janssen Pharmaceutica Nv Antagonistas del receptor de urotensina ii
JP2011529966A (ja) * 2008-08-02 2011-12-15 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ ウロテンシンｉｉ受容体拮抗物質
TW201321371A (zh) 2011-10-14 2013-06-01 Incyte Corp 做為ａｋｔ抑制劑之異吲哚啉酮及吡咯并吡啶酮衍生物
CN110038114B (zh) * 2018-01-15 2021-12-07 中国医学科学院药物研究所 一种多肽在制备预防或治疗代谢综合征药物中的用途
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