Ester nitrates derivatives of aromatic aldehydes with multiple pharmalogic properties to treat sickle cell disease

Patent metadata

Field	Value
Publication number	US-2016221978-A1
Application number	US-201414913180-A
Country	US
Kind code	A1
Filing date	Aug 21, 2014
Priority date	Aug 23, 2013
Publication date	Aug 4, 2016
Grant date	—

Abstract

The invention provides new aromatic aldehyde compounds that have greater potency in increasing the affinity of Hb for oxygen, greater potency for preventing sickling, and additional pharmacologic properties that ameliorate other symptoms of SCD. The invention further provides methods for treating SCD by providing a subject having SCD with a compound according to the invention.

First claim

1 - 57 . (canceled)

58 . A compound of the formula:

wherein R1 and R4 are the same or different and are H, OH, alkyl, alkoxy, halogen, aryl or O-aryl; and M and Q are different and are O or (CH 2 )q; and R2 and R3 are the same or different and are H or OH; and X or Y or Z are the same or different and are C or N; and n is 0-5; and p is 0-5; and q is 0-5; with the proviso that when M is O, then either n is 1-5 or R1 is not H; and salts thereof.

59 . The compound according to claim 58 , wherein R1 is H; and M is O; and R2 is H; and R3 is OH; and p is 0; and salts thereof.

60 . The compound according to claim 58 , having the following structure:

61 . The compound according to claim 58 , having the following structure:

62 . The compound according to claim 58 , having the following structure:

63 . The compound according to claim 58 , having the following structure:

64 . A method for treating a subject having sickle cell disease (SCD), comprising administering to the subject a therapeutically effective amount of a compound according to claim 58 .

65 . The method according to claim 64 , wherein the compound is

66 . The method according to claim 64 , wherein the compound is

67 . The method according to claim 64 , wherein the compound is

68 . The method according to claim 64 , wherein the compound is

69 . A compound of the formula:

wherein n is 0-5; and salts thereof.

70 . The compound according to claim 69 , having the following structure:

71 . A method for treating a subject having sickle cell disease (SCD), comprising administering to the subject a therapeutically effective amount of a compound according to claim 69 .

72 . The method according to claim 71 , wherein the compound is

73 . A compound of the formula:

wherein R1 and R4 are the same or different and are H, OH, alkyl, alkoxy, halogen, aryl or O-aryl; and M and Q are different and are O or (CH 2 )q; and R2 and R3 are the same and are ONO 2 or different with either as ONO 2 and the other as H or OH; and X or Y or Z are the same or different and are C or N; and n is 0-5; and p is 0-5; and q is 0-5; and salts thereof.

74 . The compound according to claim 73 , wherein R1 is H; and M is O; and R2 is H; and R3 is ONO 2 ; and p is 0; and salts thereof.

75 . The compound according to claim 73 , having the following structure:

76 . The compound according to claim 73 , having the following structure:

77 . The compound according to claim 73 , having the following structure:

78 . A method for treating a subject having sickle cell disease (SCD), comprising administering to the subject a therapeutically effective amount of a compound according to claim 73 .

79 . The method according to claim 78 , wherein the compound is

80 . The method according to claim 78 , wherein the compound is

81 . The method according to claim 78 , wherein the compound is

Assignees

• Univ Virginia Commonwealth

Inventors

• Safo Martin
• Venitz Jurgen
• Danso-Danquah Richmond
• Despande Tanvi
• Zhang Yan

Classifications

• C07D307/58 Primary

  One oxygen atom, e.g. butenolide · CPC title

• C07D213/30

  Oxygen atoms · CPC title