US2018362506A1PendingUtilityA1
Indole compounds and pharmaceutical use thereof
Est. expiryNov 25, 2029(~3.3 yrs left)· nominal 20-yr term from priority
Inventors:Teruhiko InoueTetsudo KayaShinichi KikuchiKoji MatsumuraRitsuki MasuoMotoya SuzukiMichihide Maekawa
C07D 413/14C07D 471/04C07D 401/14C07D 417/14C07D 405/14C07D 403/14C07D 403/04A61K 31/404A61K 31/416A61K 31/5377
60
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Claims
Abstract
Provided is an agent for the treatment or prophylaxis of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection or the like. A compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, or a solvate thereof: wherein each symbol is as described in the specification.
Claims
exact text as granted — not AI-modified1 .- 26 . (canceled)
27 . A process for producing a compound of formula [I]
or a pharmaceutically acceptable salt thereof comprising
contacting a compound of formula [1]
with a compound of formula [2]
to form a compound of formula [3]
and
converting the compound of formula [3] to the compound of formula [I],
wherein
R 1 is
(1) a hydrogen atom,
(2) a hydroxy group, or
(3) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s);
R 2 and R 3 are the same or different and each is
(1) a hydrogen atom, or
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group;
R 4 is a group selected from
which is bonded to the 5-position or the 6-position of the indole ring,
wherein
R 5 is
(1) a hydrogen atom, or
(2) a C 1-6 alkyl group, and
R 6 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group,
(c) a carboxy group,
(d) a C 1-6 alkoxy-carbonyl group,
(e) a C 6-10 aryl group,
(f) a C 6-10 aryloxy group,
(g) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s),
(h) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by C 1-6 alkyl group(s), and
(i) a 5- or 6-membered saturated heterocyclic group,
(3) a C 1-6 alkoxy group,
(4) a C 6-10 aryl group, or
(5) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group, or
R 5 and R 6 form, together with the nitrogen atom they are bonded to, a 5- or 6-membered cyclic amine, wherein said cyclic amine is optionally condensed with a 5- or 6-membered unsaturated heterocycle, that is optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkyl group,
(c) a C 1-6 alkoxy group, and
(d) a C 1-6 alkoxy-carbonyl group;
R 7 is
(1) a hydrogen atom, or
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group, and
(c) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s),
R 8 is
(1) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s),
(c) a C 3-6 cycloalkyl group optionally substituted by C 1-6 alkoxy group(s),
(d) a C 6-10 aryl group,
(e) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by oxo group(s),
(f) a 5- to 8-membered saturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(i) a hydroxy group,
(ii) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6 alkoxy group,
(iii) a C 1-6 alkoxy group, and
(iv) an oxo group,
(g) a C 3-6 cycloalkyloxy group,
(h) a C 6-10 aryloxy group,
(i) a 5- or 6-membered unsaturated heterocyclyloxy group,
(j) a 5- or 6-membered saturated heterocyclyloxy group, and
(k) an amino group optionally mono- or di-substituted by substituents selected from
(i) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group, a carboxy group and a carboxy-C 1-6 alkoxy group,
(ii) a C 1-6 alkyl-carbonyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6 alkoxy group,
(iii) a C 1-6 alkoxy-carbonyl group optionally substituted by C 6-10 aryl group(s), and
(iv) a C 3-6 cycloalkyl-carbonyl group optionally substituted by C 1-6 alkoxy group(s),
(2) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s),
(3) a C 3-6 cycloalkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group,
(4) a C 6-10 aryl group optionally substituted by C 1-6 alkyl group(s) optionally substituted by 1 to 3 halogen atoms,
(5) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s) optionally substituted by C 6-10 aryl group(s),
(6) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by C 1-6 alkyl group(s),
(7) a 5- or 6-membered saturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a C 1-6 alkyl group,
(b) a C 1-6 alkyl-carbonyl group, and
(c) an oxo group,
(8) a C 3-6 cycloalkyloxy group, or
(9) a C 6-10 aryl-carbonyl group, or
R 7 and R 8 form, together with the nitrogen atom and carbon atom they are bonded to, a 5- or 6-membered cyclic amine substituted by an oxo group and optionally further substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkyl group optionally substituted by hydroxy group(s),
(c) a C 1-6 alkoxy group, and
(d) a C 3-6 cycloalkyl group; and
R 9 and R 10 are the same or different and each is an amino-protecting group selected from the group consisting of a tert-butoxycarbonyl group, an ethoxycarbonyl group, a trityl group, a tetrahydropyranyl group, a methoxymethyl group, a 2-(trimethylsilyl)ethoxymethyl group, and a p-toluenesulfonyl group.
28 . A compound of formula [1]
wherein
R 1 is
(1) a hydrogen atom,
(2) a hydroxy group, or
(3) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s);
R 2 and R 3 are the same or different and each is
a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group; and
R 9 is an amino-protecting group selected from the group consisting of a tert-butoxycarbonyl group, an ethoxycarbonyl group, a trityl group, a tetrahydropyranyl group, a methoxymethyl group, a 2-(trimethylsilyl)ethoxymethyl group, and a p-toluenesulfonyl group.
29 . A compound of formula [2]
wherein
R 4 is a group selected from
which is bonded to the 5-position or the 6-position of the indole ring,
wherein
R 5 is
(1) a hydrogen atom, or
(2) a C 1-6 alkyl group, and
R 6 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group,
(c) a carboxy group,
(d) a C 1-6 alkoxy-carbonyl group,
(e) a C 6-10 aryl group,
(f) a C 6-10 aryloxy group,
(g) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s),
(h) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by C 1-6 alkyl group(s), and
(i) a 5- or 6-membered saturated heterocyclic group,
(3) a C 1-6 alkoxy group,
(4) a C 6-10 aryl group, or
(5) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group, or
R 5 and R 6 form, together with the nitrogen atom they are bonded to, a 5- or 6-membered cyclic amine, wherein said cyclic amine is optionally condensed with a 5- or 6-membered unsaturated heterocycle, that is optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkyl group,
(c) a C 1-6 alkoxy group, and
(d) a C 1-6 alkoxy-carbonyl group;
R 7 is
a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group, and
(c) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s),
R 8 is
(1) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s),
(c) a C 3-6 cycloalkyl group optionally substituted by C 1-6 alkoxy group(s),
(d) a C 6-10 aryl group,
(e) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by oxo group(s),
(f) a 5- to 8-membered saturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(i) a hydroxy group,
(ii) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6 alkoxy group,
(iii) a C 1-6 alkoxy group, and
(iv) an oxo group,
(g) a C 3-6 cycloalkyloxy group,
(h) a C 6-10 aryloxy group,
(i) a 5- or 6-membered unsaturated heterocyclyloxy group,
(j) a 5- or 6-membered saturated heterocyclyloxy group, and
(k) an amino group optionally mono- or di-substituted by substituents selected from
(i) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group, a carboxy group and a carboxy-C 1-6 alkoxy group,
(ii) a C 1-6 alkyl-carbonyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6 alkoxy group,
(iii) a C 1-6 alkoxy-carbonyl group optionally substituted by C 6-10 aryl group(s), and
(iv) a C 3-6 cycloalkyl-carbonyl group optionally substituted by C 1-6 alkoxy group(s),
(2) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s),
(3) a C 3-6 cycloalkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group,
(4) a C 6-10 aryl group optionally substituted by C 1-6 alkyl group(s) optionally substituted by 1 to 3 halogen atoms,
(5) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s) optionally substituted by C 6-10 aryl group(s),
(6) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by C 1-6 alkyl group(s),
(7) a 5- or 6-membered saturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a C 1-6 alkyl group,
(b) a C 1-6 alkyl-carbonyl group, and
(c) an oxo group,
(8) a C 3-6 cycloalkyloxy group, or
(9) a C 6-10 aryl-carbonyl group, or
R 7 and R 8 form, together with the nitrogen atom and carbon atom they are bonded to, a 5- or 6-membered cyclic amine substituted by an oxo group and optionally further substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkyl group optionally substituted by hydroxy group(s),
(c) a C 1-6 alkoxy group, and
(d) a C 3-6 cycloalkyl group; and
R 10 is an amino-protecting group selected from the group consisting of a tert-butoxycarbonyl group, an ethoxycarbonyl group, a trityl group, a tetrahydropyranyl group, a methoxymethyl group, a 2-(trimethylsilyl)ethoxymethyl group, and a p-toluenesulfonyl group.
30 . A compound of formula [3]
wherein
R 1 is
(1) a hydrogen atom,
(2) a hydroxy group, or
(3) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s);
R 2 and R 3 are the same or different and each is
a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group;
R 4 is a group selected from
which is bonded to the 5-position or the 6-position of the indole ring,
wherein
R 5 is
(1) a hydrogen atom, or
(2) a C 1-6 alkyl group, and
R 6 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group,
(c) a carboxy group,
(d) a C 1-6 alkoxy-carbonyl group,
(e) a C 6-10 aryl group,
(f) a C 6-10 aryloxy group,
(g) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s),
(h) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by C 1-6 alkyl group(s), and
(i) a 5- or 6-membered saturated heterocyclic group,
(3) a C 1-6 alkoxy group,
(4) a C 6-10 aryl group, or
(5) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group, or
R 5 and R 6 form, together with the nitrogen atom they are bonded to, a 5- or 6-membered cyclic amine, wherein said cyclic amine is optionally condensed with a 5- or 6-membered unsaturated heterocycle, that is optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkyl group,
(c) a C 1-6 alkoxy group, and
(d) a C 1-6 alkoxy-carbonyl group;
R 7 is
a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group, and
(c) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s),
R 8 is
(1) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s),
(c) a C 3-6 cycloalkyl group optionally substituted by C 1-6 alkoxy group(s),
(d) a C 6-10 aryl group,
(e) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by oxo group(s),
(f) a 5- to 8-membered saturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(i) a hydroxy group,
(ii) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6 alkoxy group,
(iii) a C 1-6 alkoxy group, and
(iv) an oxo group,
(g) a C 3-6 cycloalkyloxy group,
(h) a C 6-10 aryloxy group,
(i) a 5- or 6-membered unsaturated heterocyclyloxy group,
(j) a 5- or 6-membered saturated heterocyclyloxy group, and
(k) an amino group optionally mono- or di-substituted by substituents selected from
(i) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group, a carboxy group and a carboxy-C 1-6 alkoxy group,
(ii) a C 1-6 alkyl-carbonyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6 alkoxy group,
(iii) a C 1-6 alkoxy-carbonyl group optionally substituted by C 6-10 aryl group(s), and
(iv) a C 3-6 cycloalkyl-carbonyl group optionally substituted by C 1-6 alkoxy group(s),
(2) a C 1-6 alkoxy group optionally substituted by C 6-10 aryl group(s),
(3) a C 3-6 cycloalkyl group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) a C 1-6 alkoxy group,
(4) a C 6-10 aryl group optionally substituted by C 1-6 alkyl group(s) optionally substituted by 1 to 3 halogen atoms,
(5) an amino group optionally mono- or di-substituted by C 1-6 alkyl group(s) optionally substituted by C 6-10 aryl group(s),
(6) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by C 1-6 alkyl group(s),
(7) a 5- or 6-membered saturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a C 1-6 alkyl group,
(b) a C 1-6 alkyl-carbonyl group, and
(c) an oxo group,
(8) a C 3-6 cycloalkyloxy group, or
(9) a C 6-10 aryl-carbonyl group, or
R 7 and R 8 form, together with the nitrogen atom and carbon atom they are bonded to, a 5- or 6-membered cyclic amine substituted by an oxo group and optionally further substituted by 1 to 3 substituents selected from
(a) a hydroxy group,
(b) a C 1-6 alkyl group optionally substituted by hydroxy group(s),
(c) a C 1-6 alkoxy group, and
(d) a C 3-6 cycloalkyl group; and
R 9 and R 10 are the same or different and each is an amino-protecting group selected from the group consisting of a tert-butoxycarbonyl group, an ethoxycarbonyl group, a trityl group, a tetrahydropyranyl group, a methoxymethyl group, a 2-(trimethylsilyl)ethoxymethyl group, and a p-toluenesulfonyl group.Join the waitlist — get patent alerts
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