US2018346449A1PendingUtilityA1
Pyrazole compound and pharmaceutical use thereof
Est. expiryAug 31, 2031(~5.1 yrs left)· nominal 20-yr term from priority
Inventors:Tomoya MiuraYosuke OgoshiKazuhito UeyamaDai MotodaToshihiko IwayamaKoichi SuzawaHironobu NagamoriHiroshi UenoAkihiko TakahashiKazuyuki Sugimoto
A61P 9/10A61P 43/00A61P 35/00A61P 9/00A61P 3/10A61P 3/04A61P 27/02A61P 3/00A61P 13/12A61P 25/00A61P 1/10C07D 405/14C07D 405/12C07D 403/12C07D 413/12A61K 31/5377C07D 409/12C07D 403/14C07D 401/12A61K 31/454A61K 31/4155A61K 31/4178
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Claims
Abstract
wherein each symbol is the same as defined in the description; or a pharmaceutically acceptable salt thereof.
Claims
exact text as granted — not AI-modified1 . A compound or a pharmaceutically acceptable salt thereof represented by the general formula [Ib]:
wherein
Ring Cy is
(1) C 6-10 aryl,
(2) C 3-8 cycloalkyl or
(3) C 3-8 cycloalkenyl,
n1 is 0, 1, 2, 3 or 4,
R 1a is
(1) a halogen atom,
(2) hydroxy,
(3) carboxy,
(4) a C 1-6 alkyl group,
(5) a C 2-8 alkenyl group,
(6) a C 2-8 alkynyl group,
(7) a C 1-6 alkoxy group,
(8) a C 3-6 cycloalkyl group,
(9) a halo C 1-6 alkyl group,
(10) a hydroxy C 1-6 alkyl group,
(11) a C 1-6 alkoxy C 1-6 alkyl group,
(12) a halo C 1-6 alkoxy C 1-6 alkyl group,
(13) a C 1-6 alkylsulfonyl C 1-6 alkyl group,
(14) a halo C 1-6 alkylsulfonyl C 1-6 alkyl group,
(15) a halo C 1-6 alkylamino C 1-6 alkyl group,
(16) a C 3-6 cycloalkyl C 2-6 alkynyl group,
(17) a halo C 1-6 alkoxy group,
(18) a carboxy C 1-6 alkoxy group,
(19) a C 1-6 alkylsulfanyl group,
(20) a C 1-6 alkylsulfonyl group,
(21) a halo C 1-6 alkylsulfonyl group,
(22) a C 1-8 alkylcarbonyl group,
(23) a C 1-6 alkyloxycarbonyl group,
(24) a group represented by the Formula:
wherein
R 5 is
(a) a hydrogen atom or
(b) a C 1-6 alkyl group, and
R 6 is
(a) a C 1-6 alkyl group or
(b) a halo C 1-6 alkyl group,
(25) a saturated heterocyclo C 1-6 alkyl group (the saturated heterocycle is of 4-membered to 6-membered saturated heterocycle having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur) or
(26) a saturated heterocyclo oxy C 1-6 alkyl group (the saturated heterocycle is of 4-membered to 6-membered saturated heterocycle having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur),
provided when n1 is 2, 3 or 4, R 1a each is the same or different,
R 2a is
(1) a C 1-8 alkyl group,
(2) a C 3-8 cycloalkyl C 1-6 alkyl group,
(3) a C 6-10 aryl C 1-6 alkyl group,
(4) a saturated heterocyclo C 1-6 alkyl group (the saturated heterocycle is of 4-membered to 6-membered saturated heterocycle having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur),
(5) a C 3-8 cycloalkyl group,
(6) a halo C 1-6 alkyl group,
(7) a C 1-6 alkoxy C 1-6 alkyl group,
(8) a halo C 3-8 cycloalkyl group,
(9) a C 6-10 aryl group (the C 6-10 aryl group is optionally substituted by 1 to 4 substituents selected from
(a) a halogen atom,
(b) hydroxy,
(c) a C 1-6 alkyl group,
(d) a C 2-8 alkenyl group,
(e) a C 2-6 alkynyl group,
(f) a C 1-6 alkoxy group,
(g) a halo C 1-6 alkyl group,
(h) a C 1-6 alkoxy C 1-6 alkyl group,
(i) a halo C 1-6 alkoxy group,
(j) a hydroxy C 1-6 alkoxy group,
(k) a C 1-6 alkoxy C 1-6 alkoxy group,
(l) a carboxy C 1-6 alkoxy group,
(m) a C 6-10 aryl C 1-6 alkoxy group,
(n) a C 1-6 alkylsulfanyl C 1-6 alkoxy group,
(o) a C 1-6 alkylsulfonyl C 1-6 alkoxy group,
(p) a C 6-10 aryl C 1-6 alkoxy C 1-6 alkoxy group,
(q) a saturated heterocyclo C 1-6 alkoxy group (the saturated heterocycle is of 4-membered to 6-membered saturated heterocycle having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, and is optionally substituted by 1 to 2 C 1-6 alkyl groups),
(r) a saturated heterocyclo oxy group (the saturated heterocycle is a 4-membered to 6-membered saturated heterocycle having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur),
(s) a C 3-8 cycloalkyloxy group,
(t) a C 1-6 alkoxycarbonyloxy group and
(u) a C 1-6 alkylsulfonyl group), or
(10) a saturated heterocycle group (the saturated heterocycle is of 4-membered to 6-membered saturated heterocycle having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, and is optionally substituted by 1 to 4 C 1-6 alkyl groups), and
Ring Cy a is a group selected from
(1) a group represented by the Formula:
wherein
m2 is 1, 2 or 3,
m3 is 1, 2 or 3,
n3 is 1 or 2,
(2) a group represented by the Formula:
wherein
m4 is 0, 1, 2 or 3,
m5 is 0, 1 or 2,
provided sum of m4 and m5 is 1 or more,
(3) a group represented by the Formula:
wherein
m4 is 0, 1, 2 or 3,
m5 is 0, 1 or 2,
provided sum of m4 and m5 is 1 or more,
(4) a group represented by the Formula:
wherein
m6 is 0, 1 or 2,
m7 is 0, 1 or 2,
provided sum of m6 and m7 is 1 or more,
(5) a group represented by the Formula:
wherein
m6 is 0, 1 or 2,
m7 is 0, 1 or 2,
provided sum of m6 and m7 is 1 or more,
(6) a group represented by the Formula:
wherein
m8 is 1 or 2,
m9 is 1 or 2, and
(7) a group represented by the Formula:
wherein
m8 is 1 or 2,
m9 is 1 or 2,
n2 is 0, 1, 2, 3 or 4,
R 3a is
(1) hydroxy,
(2) a C 1-6 alkyl group or
(3) a hydroxy C 1-6 alkyl group,
provided when n2 is 2, 3 or 4, R 3a each is the same or different,
R 3b is
(1) hydroxy,
(2) a C 1-6 alkyl group (which optionally form a C 3-6 cycloalkyl group together with the carbon to which it is attached and the carbon adjacent thereto) or
(3) a hydroxy C 1-6 alkyl group, or
(4) when two R 3b are attached to the same carbon, they optionally form a C 3-6 cycloalkyl group together with the carbon to which they are attached,
provided, when n2 is 2, 3 or 4, each R 3b is the same or different, and
R 4b is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group,
(3) a carboxy C 1-6 alkyl group,
(4) a halo C 1-6 alkyl group or
(5) a C 1 6 alkoxy C 1-6 alkyl group.
2 . The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Ring Cy a is selected from
(1) a group represented by the Formula:
wherein
m4 is 0, 1, 2 or 3,
m5 is 0, 1 or 2,
provided sum of m4 and m5 is 1 or more,
(2) a group represented by the Formula:
wherein
m6 is 0, 1 or 2,
m7 is 0, 1 or 2,
provided sum of m6 and m7 is 1 or more,
(3) a group represented by the Formula:
wherein
m6 is 0, 1 or 2,
m7 is 0, 1 or 2,
provided sum of m6 and m7 is 1 or more,
(4) a group represented by the Formula:
wherein
m8 is 1 or 2,
m9 is 1 or 2, and
(5) a group represented by the Formula:
wherein
m8 is 1 or 2,
m9 is 1 or 2,
n2 is 0, 1, 2, 3 or 4,
R 3a is
(1) hydroxy,
(2) a C 1-6 alkyl group or
(3) a hydroxy C 1-6 alkyl group,
provided when n2 is 2, 3 or 4, each R 3a is the same or different,
R 3b is
(1) hydroxy,
(2) a C 1-6 alkyl group (which optionally form a C 3-6 cycloalkyl group together with the carbon to which it is attached and the carbon adjacent thereto) or
(3) a hydroxy C 1-6 alkyl group, or
(4) when two R 3b are attached to the same carbon, they optionally form a C 3-6 cycloalkyl group together with the carbon to which they are attached,
provided, when n2 is 2, 3 or 4, each R 3b is the same or different, and
R 4b is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group,
(3) a carboxy C 1-6 alkyl group,
(4) a halo C 1-6 alkyl group or
(5) a C 1-6 alkoxy C 1-6 alkyl group.
3 . The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Ring Cy a is selected from
(1) a group represented by the Formula:
herein,
m4 is 0, 1, 2 or 3,
m5 is 0, 1 or 2,
provided sum of m4 and m5 is 1 or more, and
(2) a group represented by the Formula:
wherein
m6 is 0, 1 or 2,
m7 is 0, 1 or 2,
provided sum of m6 and m7 is 1 or more,
n2 is 0, 1, 2, 3 or 4,
R 3a is
(1) hydroxy,
(2) a C 1-6 alkyl group or
(3) a hydroxy C 1-6 alkyl group,
provided, when n2 is 2, 3 or 4, each R 3a is the same or different,
R 3b is
(1) hydroxy,
(2) a C 1-6 alkyl group (which optionally form a C 3-6 cycloalkyl group together with the carbon to which it is attached and the carbon adjacent thereto) or
(3) a hydroxy C 1-6 alkyl group, or
(4) when two R 3b are attached to the same carbon, they optionally form a C 3-6 cycloalkyl group together with the carbon to which they are attached,
provided, when n2 is 2, 3 or 4, each R 3b is the same or different, and
R 4b is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group,
(3) a carboxy C 1-6 alkyl group,
(4) a halo C 1-6 alkyl group or
(5) a C 1-6 alkoxy C 1-6 alkyl group.
4 . The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Ring Cy a is selected from
(1) a group represented by the Formula:
wherein
n2 is 0, 1, 2, 3 or 4, and
(2) a group represented by the Formula:
wherein
n2 is 0 or 1,
R 3a is
(1) hydroxy,
(2) a C 1-6 alkyl group or
(3) a hydroxy C 1-6 alkyl group, and
R 3b is
(1) hydroxy,
(2) a C 1-6 alkyl group (which optionally form a C 3-6 cycloalkyl group together with the carbon to which it is attached and the carbon adjacent thereto) or
(3) a hydroxy C 1-6 alkyl group, or
(4) when two R 3b are attached to the same carbon, they optionally form a C 3-6 cycloalkyl group together with the carbon to which they are attached,
provided, when n2 is 2, 3 or 4, each R 3b is the same or different, and
R 4b is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group,
(3) a carboxy C 1-6 alkyl group,
(4) a halo C 1-6 alkyl group or
(5) a C 1-6 alkoxy C 1-6 alkyl group.
5 . The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4 , wherein the ring Cy is C 6-10 aryl.
6 . The compound or a pharmaceutically acceptable salt thereof according to claim 5 , wherein the ring Cy is phenyl.
7 . The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6 wherein R 1a is
(1) a halogen atom,
(2) a C 1-6 alkyl group,
(3) a C 1-6 alkoxy group,
(4) a halo C 1-6 alkyl group,
(5) a C 1-6 alkoxy C 1-6 alkyl group,
(6) a halo C 1-6 alkoxy C 1-6 alkyl group or
(7) a halo C 1-6 alkoxy group,
provided when n1 is 2, 3, or 4, R 1a each is the same or different.
8 . The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7 , wherein R 2a is a C 6-10 aryl group (the C 6-10 aryl group is optionally substituted by 1 to 4 substituents selected from
(a) a halogen atom,
(b) a C 1-6 alkyl group,
(c) a C 1-6 alkoxy group and
(d) a carboxy C 1-6 alkoxy group).
9 . The compound or a pharmaceutically acceptable salt thereof according to claim 8 , wherein R 2a is a phenyl group (the phenyl group is optionally substituted by 1 to 4 substituents selected from
(a) a halogen atom, (b) a C 1-6 alkyl group, (c) a C 1-6 alkoxy group and (d) a carboxy C 1-6 alkoxy group).
10 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is selected from the following Formulae:
11 . A pharmaceutical composition which comprises a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 and a pharmaceutically acceptable carrier.
12 . A SGLT1 inhibitor which comprises a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 .
13 . An agent for treating or preventing diabetes which comprises a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 .
14 . The agent for treating or preventing diabetes according to claim 13 , wherein diabetes is type II diabetes mellitus.
15 . A method for inhibiting SGLT1 which comprises administrating to mammals a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 .
16 . A method for treating or preventing diabetes which comprises administrating to mammals a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 .
17 . The method according to claim 16 , wherein the diabetes is type II diabetes mellitus.
18 . Use of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 for manufacturing a SGLT1 inhibitor.
19 . Use of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 for manufacturing an agent for treating or preventing diabetes.
20 . The use according to claim 19 wherein the diabetes is type II diabetes mellitus.Cited by (0)
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