US 2003/0147845 A1Published application

O2-arylated or O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates and O2-substituted 1-[(2-carboxylato) pyrrolidin-1-yl]diazen-1-ium-1,2-diolates

AssigneeThe Government of the U.S.A., The Secretary of the Department of Health and Human Services

InventorsJoseph E. Saavedra, Larry K. Keefer, Aloka Srinivasan, Christian Bogdan, William G. Rice, Xinhua Ji

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Abstract

Diazeniumdiolates, wherein the N1 position is substituted by an inorganic or organic moiety and the O2-oxygen is bound to a substituted or unsubstituted aromatic group, are provided. Also provided are O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates (O2-glycosylated diazeniumdiolates) and O2-substituted 1-[(2-carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolates (1-[(2-carboxylato)pyrrolidin-1-yl]diazeniumdiolates). The O2-aryl diazeniumdiolates are stable with respect to the hydrolytic generation of nitric oxide in neutral to acidic solutions and generate nitric oxide in basic or nucleophilic environments or microenvironments. Also provided are compositions, including pharmaceutical compositions, comprising such compounds and methods of using such compounds.

Claims69

Dependent claims

A polymer comprising a polymeric backbone and at least one functional group having the formula:

46
wherein X is selected from the group consisting of an amino, a polyamino, a C1-C24 aliphatic, a C6-C30 aryl, a C3-C30 heteroaromatic having 1 to 3 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, a C3-C30 nonaromatic cyclic, and an oximyl, and Q is selected from the group consisting of an acridinyl, an anthracenyl, a benzimidazolyl, a benzisoxazolyl, a benzofuryl, a benzothienyl, a benzoxazolyl, a benzopyrazolyl, a benzothiazolyl, a carbazolyl, a chlorophyllyl, a cinnolyl, a furyl, an imidazolyl, an indolyl, an isobenzofuryl, an isoindolyl, an isoxazolyl, an isothiazolyl, an isoquinolyl, a naphthyl, an oxazolyl, a phenanthryl, a phenanthridinyl, a phenothiazinyl, a phenoxazinyl, a phenyl, a phthalimidyl, a phthalazinyl, a phthalocyaninyl, a pteridinyl, a purinyl, which is optionally part of a nucleic acid, a ribosylpurinyl, a pyrazinyl, a pyrazolyl, a pyridazyl, a pyridyl, a pyrimidyl, which is optionally part of a nucleic acid, a ribosylpyrimidyl, a pyrrocolinyl, a pyrryl, a quinolyl, a quinoxalinyl, a quinazolinyl, a sydnonyl, a tetrazolyl, a thiazolyl, a thienyl, a thyroxinyl, a triazinyl, and a triazolyl, wherein a ring atom of Q is bonded to an oxygen atom of the at least one functional group, wherein X is bound to the polymeric backbone, and wherein X and Q are optionally substituted.

A compound having the formula:

60
wherein R is a C1-12 straight chain alkyl, a C3-12 branched chain alkyl, a C2-12 straight chain or a C3-12 branched chain olefinic, a C1-12 acyl, sulfonyl, carboxamido, a glycosyl group, a C1-C30 aryl group or a group of the formula —(CH2)n—ON═N(O)NR28R29, wherein n is an integer of 2-8, and R28 and R29 are independently a C1-12 straight chain alkyl, a C3-12 branched chain alkyl, or a C2-12 straight chain or a C3-12 branched chain olefinic, or R28 and R29, together with the nitrogen atom to which they are bonded, form a heterocyclic group selected from the group consisting of a pyrrolidino, a piperidino, a piperazino and a morpholino group;
and R22 is hydrogen, hydroxyl, OM, wherein M is a cation, a halo, X1R23R24, wherein X1 is O, N or S, and R23 and R24 are independently a C1-24 alkyl, a C3-24 cycloalkyl, a C2-24 olefinic, a C3-C30 aryl, or a heterocyclic group, and, when X1 is O or S, there is no R24.

Dependencies are inferred from the claim text.

Facts

Application: 10/337,495Filed 7 Jan 2003
Priority: 27 Sep 1996
Published: 7 Aug 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 213/64
One oxygen atom: attached in position 2 or 6
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 11/00
Drugs for disorders of the respiratory system
A61P 15/10
Drugs for genital or sexual disorders ; Contraceptives: for impotence

Family

Application60/026,816Us provisional application · filed 27 Sep 1996
Application60/045,917Us provisional application · filed 7 May 1997
Application60/051,696Us provisional application · filed 3 Jul 1997
Application09/254,301Division · filed 3 May 1999
Application09/254,301A 371 of international · filed 3 May 1999
Application10/337,495Division · filed 7 Jan 2003
US 6,610,660 B1Related patent
US 6,911,433 B2Related patent
US 2003/0147845 A1This patent

From the US filing history. Foreign family members aren’t listed.