Claims for Patent: 10,556,894

Summary for Patent: 10,556,894

Title:	Anti-HCMV compositions and methods
Abstract:	Novel compounds useful for treating and/or preventing HCMV infections are provided.
Inventor(s):	Remiszewski; Stacy (Doylestown, PA), Koyuncu; Emre (Doylestown, PA), Sun; Qun (Princeton, PA), Chiang; Lillian (Princeton, NJ)
Assignee:	Evrys Bio, LLC (Doylestown, PA)
Application Number:	15/525,504
Patent Claims:	1. A composition comprising a compound of Formula II or a pharmaceutically acceptable salt thereof: ##STR00117## wherein X.sub.1, X.sub.2, X.sub.3, and X.sub.4 are independently selected from CH and N, p is 0 or 1, R.sub.1 is H, halo, --CN, --NO.sub.2, --C(O)NR.sub.6R.sub.7, or C(O)OR.sub.6, R.sub.2 is H or a lower straight or branched alkyl or alkenyl optionally substituted with one heteroatom selected of N and O, R.sub.3 is H or OH, R.sub.6 and R.sub.7 are independently selected in each instance from H and lower straight chain or branched alkyl, when Ring A is aromatic, X.sub.5 is CH, CR.sub.1, or N, and when Ring A is not aromatic, X.sub.5 is CH.sub.2, CHR.sub.1, O, S, or NR.sub.7; with the proviso that the compound is not: ##STR00118## or a pharmaceutically acceptable salt thereof. 2. A composition comprising a compound of Formula III or a pharmaceutically acceptable salt thereof: ##STR00119## wherein X.sub.1, X.sub.2, X.sub.3, and X.sub.4 are independently selected from CH and N, p is 0 or 1, when p is 0, Z.sub.1 is CH.sub.2, when p is 1, Z.sub.1 is CH.sub.2, O, S, or NR.sub.7; R.sub.1 is H, halo, --CN, --NO.sub.2, --C(O)NR.sub.6R.sub.7, or C(O)OR.sub.6, R.sub.2 is H or a lower straight or branched alkyl or alkenyl optionally substituted with one heteroatom selected of N and O, R.sub.6 and R.sub.7 are independently selected in each instance from H and lower straight chain or branched alkyl, when Ring A is aromatic, X.sub.5 is CH, CR.sub.1, or N, and when Ring A is not aromatic, X.sub.5 is CH.sub.2, CHR.sub.1, O, S, or NR.sub.7. 3. A composition comprising a compound of Formula IV or a pharmaceutically acceptable salt thereof: ##STR00120## wherein X.sub.1, X.sub.2, X.sub.3, and X.sub.4 are independently selected from CH and N, m is 0, 1 or 2, R.sub.2 is H or a lower straight or branched alkyl or alkenyl optionally substituted with one heteroatom selected of N and O, R.sub.6 and R.sub.7 are independently selected in each instance from H and lower straight chain or branched alkyl, when m=0 or 1, Z.sub.1 is CH.sub.2, and when m=2, Z.sub.2 is CH.sub.2, O, S, or NR.sub.7. 4. A composition comprising a compound of Formula VI or a pharmaceutically acceptable salt thereof: ##STR00121## wherein X.sub.1 and X.sub.2 are independently selected from CH and N, p is 0 or 1, R.sub.1 is H, halo, --CN, --NO.sub.2, --C(O)NR.sub.6R.sub.7, or C(O)OR.sub.6, R.sub.2 is H or a lower straight or branched alkyl or alkenyl optionally substituted with one heteroatom selected of N and O, R.sub.4 is H or a saturated 5- or 6-membered aryl or cycloalkyl with up to two heteroatoms selected from N, O and S, R.sub.6 and R.sub.7 are independently selected in each instance from H and lower straight chain or branched alkyl, when Ring A is aromatic, X.sub.5 is CH, CR.sub.1, or N, and when Ring A is not aromatic, X.sub.5 is CH.sub.2, CHR.sub.1, O, S, or NR.sub.7. 5. A composition comprising a compound of Formula VII or a pharmaceutically acceptable salt thereof: ##STR00122## wherein X.sub.1 and X.sub.2 are independently selected from CH and N, p is 0 or 1, when p is 0, Z.sub.1 is CH.sub.2, when p is 1, Z.sub.1 is CH.sub.2, O, S, or NR.sub.7, R.sub.1 is H, halo, --CN, --NO.sub.2, --C(O)NR.sub.6R.sub.7, or C(O)OR.sub.6, R.sub.2 is H or a lower straight or branched alkyl or alkenyl optionally substituted with one heteroatom selected of N and O, R.sub.4 is H or a saturated 5- or 6-membered aryl or cycloalkyl with up to two heteroatoms selected from N, O and S, R.sub.6 and R.sub.7 are independently selected in each instance from H and lower straight chain or branched alkyl, when Ring A is aromatic, X.sub.5 is CH, CR.sub.1, or N, and when Ring A is not aromatic, X.sub.5 is CH.sub.2, CHR.sub.1, O, S, or NR.sub.7. 6. The composition of claim 4, wherein R.sub.4 is in the meta or para position and is selected from the group consisting of pyrrole, imidazole, pyrazole, pyrazine, pyrimidine and pyridazine. 7. A method for treating a HCMV infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula I: ##STR00123## wherein: ##STR00124## Ar is wherein each cyclic 5- or 6-membered ring in Ar optionally contains up to two N heteroatoms, Y is, independently in each instance, CH.sub.2 or a bond, Ring B is selected from the group consisting of: ##STR00125## m is 0, 1 or 2, n is, independently in each instance, 0 or 1, p is 0 or 1, when p is 0, Z.sub.1 is CH.sub.2, when p is 1, Z.sub.1 is CH.sub.2, O, S, or NR.sub.7, R.sub.1 is H, halo, --CN, --NO.sub.2, --C(O)NR.sub.6R.sub.7, or C(O)OR.sub.6, R.sub.2 is H or a lower straight or branched alkyl or alkenyl optionally substituted with one heteroatom selected of N and O, R.sub.3 is H or OH, R.sub.4 is H or a saturated 5- or 6-membered aryl or cycloalkyl with up to two heteroatoms selected from N, O and S, R.sub.5 is H, --OR.sub.7, or --NR.sub.6R.sub.7, R.sub.6 and R.sub.7 are independently selected in each instance from H and lower straight chain or branched alkyl, when Ring A is aromatic, X.sub.5 is CH, CR.sub.1, or N, when Ring A is not aromatic, X.sub.5 is CH.sub.2, CHR.sub.1, O, S, or NR.sub.7, when m=0 or 1, Z.sub.1 is CH.sub.2, and when m=2, Z.sub.2 is CH.sub.2, O, S, or NR.sub.7; or a pharmaceutically acceptable salt thereof, with the proviso that the compound is not: ##STR00126## or a pharmaceutically acceptable salt thereof. 8. The method of claim 7, wherein the compound of Formula I is a compound of Formula II or a pharmaceutically acceptable salt thereof: ##STR00127## wherein X.sub.1, X.sub.2, X.sub.3, and X.sub.4 are independently selected from CH and N, with the proviso that the compound is not: ##STR00128## or a pharmaceutically acceptable salt thereof. 9. The method of claim 7, wherein the compound of Formula I is a compound of Formula III or a pharmaceutically acceptable salt thereof: ##STR00129## wherein X.sub.1, X.sub.2, X.sub.3, and X.sub.4 are independently selected from CH and N. 10. The method of claim 7, wherein the compound of Formula I is a compound of Formula IV or a pharmaceutically acceptable salt thereof: ##STR00130## wherein X.sub.1, X.sub.2, X.sub.3, and X.sub.4 are independently selected from CH and N. 11. The method of claim 7, wherein the compound of Formula I is a compound of Formula V or a pharmaceutically acceptable salt thereof: ##STR00131## wherein X.sub.1 and X.sub.2 are independently selected from CH and N. 12. The method of claim 7, wherein the compound of Formula I is a compound of Formula VI or a pharmaceutically acceptable salt thereof: ##STR00132## wherein X.sub.1 and X.sub.2 are independently selected from CH and N. 13. The method of claim 7, wherein the compound of Formula I is a compound of Formula VII or a pharmaceutically acceptable salt thereof: ##STR00133## wherein X.sub.1 and X.sub.2 are independently selected from CH and N. 14. The method of claim 11, wherein R.sub.4 is in the meta or para position and is selected from the group consisting of pyrrole, imidazole, pyrazole, pyrazine, pyrimidine and pyridazine. 15. The method of claim 7, wherein the compound of Formula I is selected from the group consisting of: ##STR00134## ##STR00135## ##STR00136## and pharmaceutically acceptable salts thereof. 16. The method of claim 7, wherein the method further comprises administering a therapeutically effective amount of an antiviral agent. 17. The method of claim 16, wherein the antiviral agent is selected from the group consisting of: acyclovir, docosanol, ribarivin, interferons, and the like; cellulose acetate, carbopol and carrageenan, pleconaril, amantidine, amantidine, fomivirsen, zidovudine, lamivudine, zanamivir, oseltamivir, brivudine, abacavir, adefovir, amprenavir, arbidol, atazanavir, atripla, cidofovir, combivir, edoxudine, efavirenz, emtricitabine, enfuvirtide, entecavir, famciclovir, fosamprenavir, foscarnet, fosfonet, ganciclovir, gardasil, ibacitabine, imunovir, idoxuridine, imiquimod, indinavir, inosine, integrase inhibitor, lamivudine, lopinavir, loviride, mk-0518, maraviroc, moroxydine, nelfinavir, nevirapine, nexavir, nucleotide and/or nucleoside analogues, oseltamivir, penciclovir, peramivir, podophyllotoxin, rimantadine, ritonavir, saquinavir, stavudine, tenofovir, tenofovir disoproxil, tipranavir, trifluridine, trizivir, tromantadine, truvada, valaciclovir, valganciclovir, vicriviroc, vidarabine, viramidine, zalcitabine, morpholino oligonucleotides, ribozyme, protease inhibitors, an assembly inhibitor, zidovudine, brincidofovir, favipiravir, nitoxanide, letermovir, maribavir, CMX157 or a combination thereof. 18. The composition of claim 4, wherein R.sub.4 is in the meta or para position and is selected from the group consisting of pyrrole, imidazole, pyrazole, pyrazine, pyrimidine and pyridazine. 19. The composition of claim 5, wherein R.sub.4 is in the meta or para position and is selected from the group consisting of pyrrole, imidazole, pyrazole, pyrazine, pyrimidine and pyridazine. 20. The method of claim 12, wherein R.sub.4 is in the meta or para position and is selected from the group consisting of pyrrole, imidazole, pyrazole, pyrazine, pyrimidine and pyridazine. 21. The method of claim 13, wherein R.sub.4 is in the meta or para position and is selected from the group consisting of pyrrole, imidazole, pyrazole, pyrazine, pyrimidine and pyridazine. 22. The composition of claim 6, wherein the compound is selected from the group consisting of: ##STR00137## ##STR00138## and pharmaceutically acceptable salts thereof. 23. The composition of claim 1, wherein the compound is selected from the group consisting of: ##STR00139## and pharmaceutically acceptable salts thereof. 24. The composition of claim 4, wherein the compound is selected from the group consisting of: ##STR00140## and pharmaceutically acceptable salts thereof.

Details for Patent 10,556,894

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Llc	GARDASIL	human papillomavirus quadrivalent (types 6, 11, 16 and 18) vaccine, recombinant	Injection	125126	June 08, 2006	10,556,894	2040-02-29