US2012115851A1PendingUtilityA1
Compound inhibiting in vivo phosphorus transport and medicine containing the same
Est. expiryMar 27, 2023(expired)· nominal 20-yr term from priority
A61P 9/00A61P 7/00A61P 9/04A61P 3/06A61P 37/00A61P 37/04A61P 5/00A61P 9/10A61P 7/06A61P 5/18A61P 43/00A61P 25/00A61P 3/12A61P 3/10A61P 27/02C07C 323/66C07C 251/86C07D 213/82C07D 405/12C07D 213/81C07D 307/38A61P 17/04C07D 249/12C07C 323/25C07D 209/14C07D 211/46A61P 19/00C07D 307/52C07D 495/04A61P 21/00C07C 317/44C07D 333/22C07C 259/10C07D 333/68A61P 19/02C07D 333/38C07D 307/71C07C 255/66C07D 209/34A61P 15/00C07D 491/10C07C 2601/14C07D 471/04C07D 409/12A61P 13/12A61P 11/00C07C 323/60C07D 401/12C07D 213/53C07D 261/18C07D 491/113C07D 403/12C07D 333/78C07D 295/185C07D 295/155C07D 295/13C07D 257/04C07D 249/10C07D 241/44C07D 233/64C07D 231/04C07D 213/70C07D 211/60C07D 211/58C07D 211/34C07D 207/27
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Claims
Abstract
An objective of the present invention is to provide compounds that can effectively suppress the concentration of phosphorus in serum to effectively prevent or treat diseases induced by an increase in concentration of phosphate in serum. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: wherein A represents an optionally substituted five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and represents a single bond or a double bond, R 5 represents optionally substituted aryl or the like, Z represents —N═CHR 6 R 7 or the like, R 6 and R 7 represent H, optionally substituted alkyl, optionally substituted aryl or the like, R 101 and R 102 together form ═O, and R 103 and R 104 represent H, or R 101 and R 104 together from a bond, and R 102 and R 103 together form a bond.
Claims
exact text as granted — not AI-modified1 - 49 . (canceled)
50 . A compound represented by represented by formula (I-1), or a pharmaceutically acceptable salt thereof:
wherein
A represents formula (IIa):
wherein R 1 , R 2 , R 3 , and R 4 , which may be the same or different, represent
(a) a halogen atom;
(b) hydroxyl;
(c) C 1-6 alkyl;
(d) C 1-6 alkoxy;
(e) aryl;
(f) aryloxy;
(g) arylthio;
(h) alkylthio;
(i) nitro;
(j) amino;
(k) mono- or di-arylamino;
(l) mono- or di-C 1-6 alkylamino;
(m) C 2-6 alkenyl;
(n) C 2-6 alkenyloxy;
(o) C 2-6 alkenylthio;
(p) mono- or di-C 2-6 alkenylamino;
(q) carboxyl;
(r) C 1-6 alkyl- or aryl-oxycarbonyl; or
(s) a hydrogen atom,
(c) the C 1-6 alkyl group, (d) the C 1-6 alkoxy group, (e) the aryl group, (f) the aryloxy group, (g) the arylthio group, (h) the alkylthio group, (m) the C 2-6 alkenyl group, (n) the C 2-6 alkenyloxy group, and (o) the C 2-6 alkenylthio group are optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C 1-6 alkoxy, (5) C 1-6 alkylthio, (6) C 1-6 alkylsulfonyl, (7) mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C 1-6 alkyl, and the aryl group is optionally substituted by halogen, C 1-6 alkyl, C 1-6 alkoxy, or C 1-6 alkylamino, (15) C 1-6 alkoxy-(CH 2 CH 2 O) m wherein m is an integer of 1 to 6, (16) carboxyl, (17) an oxygen atom (═O), or (18) C 3-7 cycloalkyl,
the aryl moiety in (k) the mono- or di-arylamino group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C 1-6 alkoxy, (5) C 1-6 alkylthio, (6) C 1-6 alkylsulfonyl, (7) mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, (14) arylamino in which the amino group is optionally substituted by C 1-6 alkyl, and the aryl group is optionally substituted by a halogen atom, C 1-6 alkyl, C 1-6 alkoxy, or C 1-6 alkylamino, (15) C 1-6 alkoxy-(CH 2 CH 2 O) m wherein m is an integer of 1 to 6, (16) carboxyl, (17) an oxygen atom (═O), or (18) C 3-7 cycloalkyl, and, in the case of the mono-arylamino group, the amino group is optionally substituted by C 1-6 alkyl optionally substituted by hydroxyl or a halogen atom,
in (1) the mono- or di-C 1-6 alkylamino, the di-C 1-6 alkyl group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, or aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two C 1-6 alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl or a halogen atom; arylamino in which the amino group is optionally substituted by C 1-6 alkyl; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group,
in (p) the mono- or di-C 1-6 alkenylamino group, the amino group of the monoalkenylamino group is optionally substituted by C 1-6 alkyl optionally substituted by hydroxyl or a halogen atom, and the di-C 2-6 alkenyl together may form unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkenyl groups on the amino group or the unsaturated cyclic amino moiety is optionally substituted by a halogen atom; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two C 1-6 alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl or a halogen atom; arylamino in which the amino group is optionally substituted by C 1-6 alkyl; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group,
when two of R 1 , R 2 , R 3 , and R 4 are (c) C 1-6 alkyl groups or (m) C 2-6 alkenyl groups, the alkyl or the alkenyl groups together with the carbon atoms to which they are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring, and
* represents a bond to —C(═O)—NH(Z)—
---- represents a double bond,
R 5 represents optionally substituted C 5-7 cycloalkyl, optionally substituted aryl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, wherein R 5 is optionally substituted by
(I) a halogen atom;
(II) C 1-6 alkyl optionally containing a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C 1-6 alkoxy, (5) C 1-6 alkylthio, (6) C 1-6 alkylsulfinyl, (7) C 1-6 alkylsulfonyl, (8) mono- or di C 1-6 alkylamino, (8′) amino substituted by a heterocyclic group optionally substituted by C 1-6 alkyl, (9) C 1-6 alkylcarbonyloxy, (10) C 1-6 alkylcarbonylthio, (11) C 1-6 alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C 1-6 alkyl- or aryl-sulfonylamino, (18) C 1-6 alkyl- or aryl-ureido, (19) C 1-6 alkoxy- or aryloxy-carbonylamino, (20) C 1-5 alkylamino- or arylaminocarbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S(═O)j wherein Het represents a heterocyclic group, j is 0, 1, or 2, and the Het is optionally substituted by alkyl optionally substituted by mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl, (24) cyano, and (25) a halogen atom, wherein the alkyl moiety in (4) the C 1-6 alkoxy group, (5) the C 1-6 alkylthio group, (6) the C 1-6 alkylsulfinyl group, and (7) the C 1-6 alkylsulfonyl group is optionally substituted by a halogen atom; C 1-6 alkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; aryloxy; arylthio; hydroxyl; carboxyl; —S(═O) 2 (—OH); C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl; or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxy, and
in (8) the mono- or di-C 1-6 alkylamino group, the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C 1-6 alkyl; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, and, when one carbon atom in the cyclic amino moiety is substituted by two C 1-6 alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH2) p —O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group;
(III) C 1-6 alkoxy optionally substituted by a halogen atom;
(IV) C 1-6 alkylthio optionally substituted by a halogen atom;
(V) C 3-7 cycloalkyl;
(VI) aryl;
(VII) aryloxy;
(VIII) C 1-6 alkylcarbonylamino;
(VIX) C 1-6 alkylcarbonyloxy;
(X) hydroxyl;
(XI) nitro;
(XII) cyano;
(XIII) amino;
(XIV) mono or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms;
(XV) arylamino;
(XVI) C 1-6 alkyl- or aryl-sulfonylamino;
(XVII) C 1-6 alkyl- or aryl-ureido;
(XVIII) C 1-6 alkoxy- or aryloxy-carbonylamino;
(XIX) C 1-6 alkylamino- or arylamino-carbonyloxy;
(XX) C 1-6 alkoxy- or aryloxy-carbonyl;
(XXI) acyl;
(XXII) carboxyl;
(XXIII) carbamoyl;
(XXIV) mono- or di-alkylcarbamoyl;
(XXV) a heterocyclic group;
(XXVI) alkyl- or aryl-sulfonyl;
(XXVII) C 2-6 alkenyloxy group; or
(XXVIII) C 2-6 alkenyloxy,
Z represents group (A) or group (B):
wherein
R 6 represents a hydrogen atom or C 1-6 alkyl,
R 7 represents optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted aryl C 2-6 alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, wherein R 7 is optionally substituted by.
(I) a halogen atom;
(II) C 1-6 alkyl optionally having a substituent selected from a group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C 1-6 alkoxy, (5) C 1-6 alkylthio optionally substituted by hydroxyl, (6) C 1-6 alkylsulfinyl, (7) C 1-6 alkylsulfonyl, (8) mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (9) C 1-6 alkylcarbonyloxy, (10) C 1-6 alkylcarbonylthio, (11) C 1-6 alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C 1-8 alkyl- or aryl-sulfonylamino, (18) C 1-6 alkyl- or aryl-ureido, (19) C 1-6 alkoxy- or aryloxy-carbonylamino, (20) C 1-6 alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S— wherein Het represents a heterocyclic group, (24) cyano, (25) a halogen atom, and (26) C 1-6 alkyl- or aryl-oxycarbonyl;
(III) C 1-6 alkoxy optionally having a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C 1-6 alkoxy, (5) C 1-6 alkylthio optionally substituted by hydroxyl, (6) C 1-6 alkylsulfinyl, (7) C 1-6 alkylsulfonyl, (8) mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (9) C 1-6 alkylcarbonyloxy, (10) C 1-6 alkylcarbonylthio, (11) C 1-6 alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C 1-6 alkyl- or aryl-sulfonylamino, (18) C 1-8 alkyl- or aryl-ureido, (19) C 1-6 alkoxy- or aryloxy-carbonylamino, (20) C 1-6 alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S— wherein the Het represents a heterocyclic group, (24) cyano, (25) a halogen atom, and (26) C 1-6 alkyl- or aryl-oxycarbonyl;
(IV) C 1-6 alkylthio optionally substituted by a halogen atom;
(V) C 3-7 cycloalkyl;
(VI) aryl;
(VII) aryloxy;
(VIII) C 1-6 alkylcarbonylamino;
(VIX) C 1-6 alkylcarbonyloxy;
(X) hydroxyl;
(XI) nitro;
(XII) cyano;
(XIII) amino;
(XIV) mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms;
(XV) arylamino;
(XVI) C 1-6 alkyl- or aryl-sulfonylamino;
(XVII) C 1-6 alkyl- or aryl-ureido;
(XVIII) C 1-6 alkoxy- or aryloxy-carbonylamino;
(XIX) C 1-6 alkylamino- or arylamino-carbonyloxy;
(XX) C 1-6 alkoxy- or aryloxy-carbonyl;
(XXI) aryl;
(XXII)carboxyl;
(XXIII) carbamoyl;
(XXIV) mono- or di-alkylcarbamoyl;
(XXV) a heterocyclic groups;
(XXVI) alkyl- or aryl-sulfonyl;
(XXVII) C 2-6 alkenyloxy; or
(XXVIII) C 2-6 alkynyloxy,
R 17 represents a hydrogen atom.
51 - 55 . (canceled)
56 . The compound according to claim 50 , wherein R 5 represents formula (IIIa), formula (IIIb), or formula (IIIc)
wherein
D, E, J, L, and M, which may be the same or different, represent a carbon or nitrogen atom,
G represents an oxygen or sulfur atom,
R 8 , R 9 , R 10 , R 11 , and R 12 , which may be the same or different, represent
(I) a halogen atom;
(II) C 1-6 alkyl optionally containing a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C 1-6 alkoxy, (5) C 1-6 alkylthio, (6) C 1-6 alkylsulfinyl, (7) C 1-6 alkylsulfonyl, (8) mono- or di-C 1-6 alkylamino, (8′) amino substituted by a heterocyclic group optionally substituted by C 1-6 alkyl, (9) C 1-6 alkylcarbonyloxy, (10) C 1-6 alkylcarbonylthio, (11) C 1-6 alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C 1-6 alkyl- or aryl-sulfonylamino, (18) C 1-6 alkyl- or aryl-ureido, (19) C 1-6 alkoxy- or aryloxy-carbonylamino, (20) C 1-6 alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S(═O)j- wherein the Het represents a heterocyclic group, j is 0, 1, or 2, and Het is optionally substituted by alkyl optionally substituted by mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl, (24) cyano, and (25) a halogen atom,
wherein the alkyl moiety in (4) the C 1-6 alkoxy group, (5) the C 1-6 alkylthio group, (6) the C 1-6 alkylsulfinyl group, and (7) the C 1-6 alkylsulfonyl group is optionally substituted by a hydrogen atom; a halogen atom; C 1-6 alkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; aryloxy; arylthio; hydroxyl; carboxyl; —S(═O) 2 (—OH); C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl; or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxy, and
in (8) the mono- or di-C 1-6 alkylamino group, the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C 1-6 alkyl; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, and, when one carbon atom in the cyclic amino moiety is substituted by two C 1-6 alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH 2 ) p —O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group;
(III) C 1-6 alkoxy optionally substituted by a halogen atom;
(IV) C 1-6 alkylthio optionally substituted by a halogen atom;
(V) C 3-7 cycloalkyl;
(VI) aryl;
(VII) aryloxy;
(VIII) C 1-6 alkylcarbonylamino;
(VIX) C 1-6 alkylcarbonyloxy;
(X) hydroxyl;
(XI) nitro;
(XII) cyano;
(XIII) amino;
(XIV) mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms;
(XV) arylamino;
(XVI) C 1-6 alkyl- or aryl-sulfonylamino;
(XVII) C 1-6 alkyl- or aryl-ureido;
(XVIII) C 1-6 alkoxy- or aryloxy-carbonylamino;
(XIX) C 1-6 alkylamino- or arylamino-carbonyloxy;
(XX) C 1-6 alkoxy- or aryloxy-carbonyl;
(XXI) acyl;
(XXII) carboxyl;
(XXIII) carbamoyl;
(XXIV) mono- or di-alkylcarbamoyl;
(XXV) a heterocyclic group;
(XXVI) alkyl- or aryl-sulfonyl;
(XXVII) C 2-6 alkenyloxy;
(XXVIII) C 2-6 alkynyloxy; or
(XXIX) a hydrogen atom, and
when D, E, J, L, or M represents a nitrogen atom, R 8 , R 9 , R 10 , R 11 , and R 12 each are absent, or otherwise may combine with a nitrogen atom to form N-oxide (N→O).
57 . The compound according to claim 50 , wherein A represents formula (IIa):
wherein
(1) R 1 , R 2 , R 3 , and R 4 represent a hydrogen atom,
(2) R 1 and R 4 represent a hydrogen atom, any one of R 2 and R 3 represents a halogen atom; hydroxyl; optionally substituted C 1-6 alkyl; optionally substituted C 1-6 alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C 1-6 alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; or optionally substituted mono- or di-C 2-6 alkenylamino in which the di-C 2-6 alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom,
(3) R 1 and R 4 represent a hydrogen atom, and R 2 and R 3 , which may be the same or different, represent a halogen atom; hydroxyl; optionally substituted C 1-6 alkyl; or optionally substituted C 1-6 alkoxy,
(4) R 1 and R 4 represent a hydrogen atom, and R 2 and R 3 together with the carbon atoms to which they are respectively attached form an unsaturated five- to seven-membered carbocyclic ring,
(5) R 1 and R 4 represent a hydrogen atom, any one of R 2 and R 3 represents optionally substituted mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, or
(6) R 1 and R 4 represent a hydrogen atom, any one of R 2 and R 3 represents optionally substituted C 1-6 alkoxy, and the other represents a hydrogen atom, and
* represents a bond to —C(═O)—NH(—Z)
R 5 represents formula (IIIa)
wherein
(i) D, E, J, L, and M represent a carbon atom, any one or two of R 8 , R 9 , R 10 , R 11 , and R 12 , which may be the same or different, represent a halogen atom; hydroxymethyl; C 1-6 alkyl optionally substituted by a halogen atom; or C 1-6 alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom,
(ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R 8 , R 9 , R 10 , R 11 , and R 12 may be the same or different and represent a halogen atom; hydroxymethyl; C 1-6 alkyl optionally substituted by a halogen atom, or C 1-6 alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom,
(iii) D, E, J, L, and M represent a carbon atom, R 8 , R 9 , and R 12 represent a hydrogen atom, any one of R 10 and R 11 represents a group of formula (IV)
—CH 2 -Q—X1-R 13 (IV)
wherein
Q represents an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl,
X1 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,
R 13 represents a hydrogen atom, a halogen atom, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, aryloxy, arylthio, hydroxyl, carboxyl, —S(═O) 2 (—OH), C 1-6 alkoxy- or aryloxy-carbonyl, C 1-6 alkylcarbonyl, aryl, or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl;
or a group of formula (V)
wherein
X2 represents a bond or straight chain or branched chain alkylene having 1 to carbon atoms,
X3 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,
R 14 and R 15 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C 1-6 alkyl; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, provided that, when X2 represents a bond, R 14 represents a hydrogen atom, or when X3 represents a bond, R 15 represents a hydrogen atom, or
R 14 and R 15 together with a nitrogen atom to which they are respectively attached to may form a heterocyclic group that may contain 1 to 3 heteroatoms in addition to the nitrogen atom, to which R 14 and R 15 are attached, and is optionally substituted by hydroxyl; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; a saturated or unsaturated five- or six-membered heterocyclic group; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; phenyl; or an oxygen atom (═O), and, when one carbon atom in the cyclic amino moiety is substituted by two C 1-6 alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH 2 ) p —O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group;
and the other represents a hydrogen atom, or
(iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R 8 , R 9 , and R 12 represent a hydrogen atom, and one of R 10 and R 11 represents a group of formula (IV)
—CH 2 -Q-X1-R 13 (IV)
wherein
Q represents an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl,
X1 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,
R 13 represents a hydrogen atom, a halogen atom, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, aryloxy, arylthio, hydroxyl, carboxyl, —S(═O) 2 (—OH), C 1-6 alkoxy- or aryloxy-carbonyl, C 1-6 alkylcarbonyl, aryl, or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl;
or a group of formula (V)
wherein
X2 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,
X3 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,
R 14 and R 15 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C 1-6 alkyl; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, provided that, when X2 represents a bond, R 14 represents a hydrogen atom, or when X3 represents a bond, R 15 represents a hydrogen atom, or
R 14 and R 15 together with a nitrogen atom to which they are respectively attached to may form a heterocyclic group that may contain 1 to 3 heteroatoms in addition to the nitrogen atom, to which R 14 and R 15 are attached, and is optionally substituted by hydroxyl; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; a saturated or unsaturated five- or six-membered heterocyclic group; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; phenyl; or an oxygen atom (═O), and, when one carbon atom in the cyclic amino moiety is substituted by two C 1-6 alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH 2 ) p —O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group;
and the other represents a hydrogen atom,
Z represents group (A), group (B), or group (C):
wherein
R 6 represents a hydrogen atom or C 1-6 alkyl,
R 7 represents optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted aryl C 2-6 alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and
R 17 represents a hydrogen atom.
58 . The compound according to claim 50 , wherein A represents formula (IIa)
wherein
(1) R 1 , R 2 , R 3 , and R 4 represent a hydrogen atom,
(2) R 1 and R 4 represent a hydrogen atom, any one of R 2 and R 3 represents a halogen atom; hydroxyl; optionally substituted C 1-6 alkyl; optionally substituted C 1-6 alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C 1-6 alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; or optionally substituted mono- or di-C 2-6 alkenylamino in which the di-C 2-6 alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom,
(3) R 1 and R 4 represent a hydrogen atom, and R 2 and R 3 , which may be the same or different, represent a halogen atom; hydroxyl; optionally substituted C 1-6 alkyl; or optionally substituted C 1-6 alkoxy,
(4) R 1 and R 4 represent a hydrogen atom, and R 2 and R 3 together with the carbon atoms to which they are respectively attached form an unsaturated five- to seven-membered carbocyclic ring,
(5) R 1 and R 4 represent a hydrogen atom, any one of R 2 and R 3 represents optionally substituted mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, or
(6) R 1 and R 4 represent a hydrogen atom, any one of R 2 and R 3 represents optionally substituted C 1-6 alkoxy, and the other represents a hydrogen atom, and
* represents a bond to —C(═O)—NH(—Z)
R 5 represents formula (IIIb) or formula (IIIc)
wherein
(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R 8 , R 9 , and R 10 , which may be the same or different, represent a halogen atom; hydroxymethyl; C 1-6 alkyl optionally substituted by a halogen atom; or C 1-6 alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or
(ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R 8 , R 9 , and R 10 represents a group of formula (IV)
—CH 2 -Q-X1-R 13 (IV)
wherein
Q represents an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl,
X1 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,
R 13 represents a hydrogen atom, a halogen atom, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, aryloxy, arylthio, hydroxyl, carboxyl, —S(═O) 2 (—OH), C 1-6 alkoxy- or aryloxy-carbonyl, C 1-6 alkylcarbonyl, aryl, or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl;
or a group of formula (V)
wherein
X2 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,
X3 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,
R 14 and R 15 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; C 1-6 alkoxy; C 1-6 alkylthio; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C 1-6 alkyl; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C 1-6 alkoxy- or aryloxy-carbonyl; C 1-6 alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, provided that, when X2 represents a bond, R 14 represents a hydrogen atom, or when X3 represents a bond, R 15 represents a hydrogen atom, or
R 14 and R 15 together with a nitrogen atom to which they are respectively attached to may form a heterocyclic group that may contain 1 to 3 heteroatoms in addition to the nitrogen atom, to which R 14 and R 15 are attached, and is optionally substituted by hydroxyl; C 1-6 alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C 1-6 alkyl, or C 1-6 alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C 1-6 alkyl groups, they together may form C 3-7 cycloalkyl; mono- or di-C 1-6 alkylamino in which the di-C 1-6 alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; a saturated or unsaturated five- or six-membered heterocyclic group; mono- or di-C 1-6 alkylcarbamoylmethyl in which the di-C 1-6 alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; phenyl; or an oxygen atom (═O), and, when one carbon atom in the cyclic amino moiety is substituted by two C 1-6 alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH 2 ) p —O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group;
and the others represent a hydrogen atom,
Z represents group (A), group (B), or group (C):
wherein
R 6 represents a hydrogen atom or C 1-6 alkyl,
R 7 represents optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted aryl C 2-6 alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and
R 17 represents a hydrogen atom.
59 - 65 . (canceled)
66 . A pharmaceutical composition comprising as an active ingredient a compound according to claim 50 or a pharmaceutically acceptable salt thereof.
67 - 86 . (canceled)
87 . A method for preventing or treating a disease for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically effective, said method comprising the step of administering a therapeutically or prophylactically effective amount of a compound according to claim 50 or a pharmaceutically acceptable salt thereof to a mammal.
88 . The method according to claim 87 , wherein the disease for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically or prophylactically effective is hyperphosphatemia.
89 . The method according to claim 87 , wherein the disease for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically or prophylactically effective is renal failure or chronic renal failure.
90 . The method according to claim 87 , wherein the diseases for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically or prophylactically effective are secondary hyperparathyroidism and primary hyperparathyroidism and diseases related thereto.
91 - 96 . (canceled)Join the waitlist — get patent alerts
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