Moncyclic L-nucleosides analogs

• US 6,552,183 B1
• Filed: 08/07/2000
• Issued: 04/22/2003
• Est. Priority Date: 10/16/1996
• Status: Expired due to Term

• Current Assignee: Ribapharm Inc. (Bausch Health Cos., Inc.)
• Original Assignee: ICN Pharmaceuticals, Inc (Bausch Health Cos., Inc.)
• Inventors: Ramasamy, Kandasamy, Tam, Robert, Averett, Devron
• Primary Examiner(s): Geist, Gary
• Assistant Examiner(s): Crane, L Eric
• Application Number:
  US09/633,493
• Time in Patent Office: 988 Days
• Field of Search: 514/43, 514/49, 514/50, 536/28-- 2, 536/28.53, 536/28.6, 536/28.7, 536/28.8, 544/224, 548/252.2, 548/255, 548/300.1, 548/356.1, 548/400
• US Class Current: 536/28.6
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom

Abstract

Novel monocyclic L-Nucleoside compounds have the general formula

Embodiments of these compounds are contemplated to be useful in treating a wide variety of diseases including infections, infestations, neoplasms, and autoimmune diseases. Viewed in terms of mechanism, embodiments of the novel compounds show immunomodulatory activity, and are expected to be useful in modulating the cytokine pattern, including modulation of Th1 and Th2 response.

Claims

1. A compound having a structure according to Formula III:

wherein;

X is independently O, S, CH₂ and NR, where R is COCH₃;

R′ and

R″

are independently selected from the group consisting of H, CN, C(═

O)NH₂, NH₂, C(═

S)NH₂, C(═

NH)NH₂.HCl, C(═

NOH)NH₂, C(═

NH)OMe, a halogen, lower alkyl and a lower alkyl aryl;

R₁ and R₄ are independently selected from the group consisting of H, CN, N₃, CH₂OH, lower alkyl and a lower alkyl amino; and

R₂, R₃, R₅, R₆, R₇ and R₈ are independently selected from the group consisting of H, OH, CN, N₃, a halogen, CH₂OH, NH₂, OCH₃, NHCH₃, ONHCH₃, SCH₃, SPh, alkenyl, lower alkyl, and a lower alkyl amino, with the proviso that when R₂═

R₃═

H, then each of R₇ and R₈ is a hydrogen or taken together are a π

-bond; and

where in compounds of Formula III, R′

is carboxamide or CN and R″

is hydrogen or a halogen;

R₁═

R₄═

R₅═

R₇═

R₈ H and R₂═

R₃═

OH, and X is oxygen.

2. A compound having a structure according to Formula IV:

wherein;

A is independently selected from the group consisting of N and C;

B, T, E and J are independently selected from the group consisting of CH, CO, N, S, NR^1′

, CCONH₂, CCH₃, and C-R^b′

;

R^a′

is independently H, lower alkyl, a lower alkylamine, COCH₃, lower alkyl alkenyl, lower alkyl vinyl or a lower alkyl aryl;

R^b′

is independently H, OH, a halogen, CN, N₃, NH₂, C(═

O)NH₂, C(═

S)NH₂, C(═

NH)NH₂.HCl, C(═

NOH)NH₂, C(═

NH)OMe, lower alkyl, a lower alkylamine, lower alkyl alkenyl, lower alkyl vinyl, or a lower alkyl aryl;

X is independently O or NR;

where R is COCH₃;

R₁ and R₄ are independently selected from the group consisting of H, CN, N₃, CH₂OH, lower alkyl and a lower alkyl amino; and

R₂, R₃, R₅, R₆, R₇ and R₈ are independently selected from the group consisting of H, OH, CN, N₃, a halogen, NH₂, CH₂OH, OCH₃, NHCH₃, ONHCH₃, SCH₃, SPh, alkenyl, allyl, lower alkyl, and a lower alkyl amino, with the proviso that when R₂═

R₃═

H, then R₇ and R₈ are a hydrogen or taken together are a π

-bond;

such that

when A is carbon;

B═

E═

N;

T is N—

Ph, then J is CO, N, S, NR^a′

, CCONH₂, CCH₃, and C-R^b′

;

R^a′

is independently H, lower alkyl, a lower alkylamine, COCH₃, lower alkyl alkenyl, lower alkyl vinyl or a lower alkyl aryl;

R^b′

is independently H, OH, a halogen, CN, N₃, NH₂, C(═

O)NH₂, C(═

S)NH₂, C(═

NH)NH₂.HCl, C(═

NOH)NH₂, C(═

NH)OMe, lower alkyl, a lower alkylamine, lower alkyl alkenyl, lower alkyl vinyl, or a lower alkyl aryl;

when A═

N;

T is CH;

B═

E═

C—

CH₃, then J is CO, CN, S, NR^a′

, CCONH₂, CCH₃, and C-R^b′

;

R^a′

is independently H, lower alkyl, a lower alkylamine, COCH₃, lower alkyl alkenyl, lower alkyl vinyl or a lower alkyl aryl;

R^2′

is independently H, OH, a halogen, CN, N₃, NH₂, C(═

O)NH₂, C(═

S)NH₂, C(═

NH)NH₂.HCl, C(═

NOH)NH₂, C(═

NH)OMe, lower alkyl, a lower alkylamine, lower alkyl alkenyl, lower alkyl vinyl, or a lower alkyl aryl;

when A is carbon, B═

N;

T═

C—

CONH₂;

E═

CH;

J=S, then X is O or NR;

where R is COCH₃; and

where in compounds of Formula IV, R¹ is H, lower alkyl or allyl;

R₂ is H, OH, a halogen, CN, N₃, NH₂, C(═

O)NH₂, C(═

S)NH₂, C(═

NH)NH₂.HCl, C(═

NOH)NH₂ or C(═

NH)OMe; and

when R₁═

R₄═

R₅═

R₇═

R₈═

H, then R₂═

R₃═

OH and X is oxygen.