Back to results
US 2010/0143300 A1Published application
Hepatitis c therapies
AssigneeBioCryst Pharmaceuticals, Inc.
InventorsYarlagadda S. Babu, Pooran Chand, Minwan Wu, Pravin L. Kotian, V. Satish Kumar, Tsu-Hsing Lin, Yahya El-Kattan, Ajit K. Ghosh
Life of this patent
Estimating the term…
Abstract
The invention provides methods for treating hepatitis C viral infections and related viral infections, as well as compounds and compositions that are useful for treating such infections.
Claims48
A compound of the formula:
- wherein:
- R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
- n is 0, 1, 2, 3, 4, or 5;
- R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
- R2 is H and R3 is OH;
- or R2 is OH and R3 is H;
- R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
- R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
- Ra, Rb, Rc, and Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
- or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
- or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
- Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
- and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
- or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
- which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
- wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
- and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
- or a pharmaceutically acceptable salt or prodrug thereof.
15 more elements
A method for treating a viral infection selected from hepatitis B, hepatitis C, Polio, Coxsackie A and B, Rhino, Echo, small pox, Ebola, and West Nile in an animal, comprising administering to the animal an effective amount of a compound of formula I:
- wherein:
- X═N or CH;
- Y═O, S or N—R4;
- R is OR3, SR3, NR3R4, NR3NR4R5, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHR3)CO2R4, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COOR3, CONR3R4, NHC(═NR3)NHR4, NR3OR4, NR3NO, NHCONHR3, NR3N═NR4, NR3N═CHR4, NR3C(O)NR4R5, NR3C(S)NR4R5, NR3C(O)OR4, CH═N—OR3, NR3C(═NH)NR4R5, NR3C(O)NR4NR5R6, O—C(O)R3, OC(O)—OR3, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONR3R4, SNR3R4, S—ONR3R4, or SO2NR3R4;
- n is 0, 1, 2, 3, 4, or 5;
- R1 is H, NR3R4, Cl, F, OR3, SR3, NHCOR3, NHSO2R3, NHCONHR3, CN, alkyl, aryl, ONR3R4, or NR3C(O)OR4;
- R2 is ribose, 2-deoxyribose;
- 2-deoxy-2-fluororibose;
- arabinose;
- 2-deoxy-2-fluoroarabinose;
- 2,3-dideoxyribose;
- 2,3-dideoxy-2-fluoroarabinose;
- 2,3-dideoxy-3-fluororibose;
- 2,3-dideoxy-2,3-didehydroribose;
- 2,3-dideoxy-3-azidoribose;
- 2,3-dideoxy-3-thiaribose;
- or 2,3-dideoxy-3-oxaribose;
- R3 is H, alkyl, aryl, F, Cl, CN, CO2H or NH2;
- and
- R4 is H, OH, alkyl, aryl, —COO-alkyl, CONH2, CONH-alkyl, O—C(O)-alkyl, O—C(O)-aryl or alkoxy;
- R3, R4, R5, and R6 are independently selected from the group consisting of H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, heterocyclic, aryl, substituted aryl, acyl, substituted acyl, SO2-alkyl OH, —COO-alkyl, CONH2, CONH-alkyl, O—C(O)-alkyl, O—C(O)-aryl alkoxy and NO;
- or R3 and R4 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
- or R4 and R5 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
- wherein any ring formed by R3 and R4 or R4 and R5 is optionally substituted with one or more hydroxyl, halo, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl;
- and
- Ra, Rb, and Rc are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
- or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
- or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
- or a pharmaceutically acceptable salt or prodrug thereof.
26 more elements
Dependencies are inferred from the claim text.