VIRAL INHIBITORS, THE SYNTHESIS THEREOF, AND INTERMEDIATES THERETO
The present disclosure discloses compositions comprising maribavir, methods of providing the same, and compositions providing intermediates useful in providing maribavir.
1 . A method of treating a patient with post-transplant cytomegalovirus (CMV) infection and/or disease, the method comprising:
administering to the patient a pharmaceutical composition comprising maribavir, or a pharmaceutically acceptable salt thereof, in an amount of about 400 mg orally twice daily,
wherein the patient is a transplant recipient, wherein the CMV infection and/or disease is refractory to treatment with ganciclovir, valganciclovir, cidofovir or foscarnet,
wherein the pharmaceutical composition comprises:
(i) maribavir:
or a pharmaceutically acceptable salt thereof; and
(ii) one or more of the following, relative to maribavir:
about 0.01% to about 0.1% w/w of Compound 2,
or a pharmaceutically acceptable salt thereof;
about 0.01% to about 0.1% w/w of Compound 3,
or a pharmaceutically acceptable salt thereof; or
about 0.01% to about 0.1% w/w of Compound 4:
or a pharmaceutically accept salt thereof.
2 . (canceled)
3 . The method according to claim 1 , wherein the patient has undergone a hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT).
4 - 24 . (canceled)
25 . The method according to claim 1 , wherein maribavir is crystal Form VI having a particle size distribution (PSD) of d(50) less than about 400 μm.
26 . The method according to claim 1 , wherein maribavir is crystal Form VI having a particle size distribution (PSD) of d(50) between about 170 and about 350 μm.
27 . The method according to claim 1 , wherein maribavir is crystal Form VI having a particle size distribution (PSD) of d(50) between about 170 and about 226 μm.
28 . The method according to claim 1 , wherein maribavir is crystal Form VI having a particle size distribution (PSD) of d(50) between about 227 and about 280 μm.
29 . The method according to claim 1 , wherein maribavir is crystal Form VI having a particle size distribution (PSD) of d(50) between about 281 and about 336 μm.
30 . The method according to claim 1 , wherein the pharmaceutical composition further comprises about 0.01% to about 0.5% w/w of D-maribavir,
or a pharmaceutically acceptable salt thereof.
31 . The method according to claim 30 , wherein the pharmaceutical composition further comprises less than 0.1% of D-maribavir, or a pharmaceutically acceptable salt thereof.
32 . The method according to claim 1 , wherein the pharmaceutical composition comprises about 0.1%, about 0.05%, about 0.02%, or about 0.01% (w/w HPLC) of compound 4, relative to maribavir.
33 . The method according to claim 1 , wherein the pharmaceutical composition comprises about 0.1% (w/w HPLC) of compound 4, relative to maribavir.
34 . The method according to claim 1 , wherein the pharmaceutical composition comprises about 0.05 (w/w HPLC) of compound 4, relative to maribavir.
35 . The method according to claim 1 , wherein the pharmaceutical composition comprises about 0.02% (w/w HPLC) of compound 4, relative to maribavir.
36 . The method according to claim 1 , wherein the pharmaceutical composition comprises about 0.01% (w/w HPLC) of compound 4, relative to maribavir.