Azaadamantane derivatives and methods of use

A compound of formula (VI)

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• L1 is —O— or —NRa—;
• A is —Ar1, —Ar2-L2-Ar3 or —Ar4-L3-Ar5;
• Ar1 is aryl or heteroaryl;
• Ar2 is aryl or monocyclic heteroaryl;
• Ar3 is aryl or heteroaryl;
• Ar4 is bicyclic heteroaryl;
• Ar5 is aryl or heteroaryl;
• L2 is a bond, —O—, —NRa—, —CH2—, or —C(O)NRa—;
• L3 is a bond, —O—, —NRc— or CH1—;
• and
• Ra is hydrogen or alkyl.

A compound of formula (VII)

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• L1 is —O— or —NRa—;
• A is —Ar1, Ar2-L2-Ar3 or —Ar4-L3-Ar5;
• Ar1 is aryl or heteroaryl;
• Ar2 is aryl or monocyclic heteroaryl;
• A3 is aryl or heteroaryl;
• Ar4 is bicyclic heteroaryl;
• Ar5 is aryl or heteroaryl;
• L2 is a bond, —O—, —NRa—, CH2—, or —C(O)NRa—;
• L3 is a bond, —O—, —NRa— or —CH2—;
• and
• Ra is hydrogen or alkyl.

A crystalline salt (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane identified by powder X-ray diffraction wherein the salt is:

• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane L-bitartrate anhydrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 4.96±0.20, 9.99±0.20, 11.77±0.20, 14.62±0.20, 14.99±0.20, 18.14±0.20, 18.44±0.20, 19.48±0.20, 20.05±0.20, 21.02±0.20, 21.38±0.20, 22.76±0.20, 24.74±0.20, 26.65±0.20, and 32.19±0.20;
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane L-bitartrate hydrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 4.63±0.20, 9.26±0.20, 13.43±0.20, 13.91±0.20, 15.98±0.20, 17.86±0.20, 21.36±0.20, and 22.33±0.20;
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane dihydrogen phosphate anhydrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 5.14±0.20, 10.31±0.20, 11.20±0.20, 13.17±0.20, 13.47±0.20, 15.61±0.20, 16.69±0.20, 17.27±0.20, 17.50±0.20, 18.56±0.20, 18.90±0.20, 19.41±0.20, 20.93±0.20, 21.80±0.20, 22.53±0.20, 23.96±0.20, 26.01±0.20, and 26.44±0.20;
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane dihydrogen phosphate hydrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 5.28±0.20, 9.82±0.20, 10.61±0.20, 13.79±0.20, 14.24±0.20, 15.13±0.20, 16.65±0.20, 16.95±0.20, 18.35±0.20, 19.52±0.20, 19.84±0.20, 21.55±0.20, 23.85±0.20, 24.26±0.20, and 25.80±0.20;
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane bisuccinate anhydrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 12.53±0.20, 13.50±0.20, 14.76±0.20, 16.98±0.20, 18.07±0.20, 18.34±0.20, 18.35±0.20, 18.88±0.20, 19.62±0.20, 19.67±0.20, 20.00±0.20, 20.71±0.20, 23.64±0.20, 23 96±0.20, 25.61±0.20, and 36.29±0.20;
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane bisuccinate hydrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 8.92±0.20, 10.94±0.20, 11.71±0.20, 13.41±0.20, 14.90±0.20, 17.61±0.20, 17.92±0.20, 18.19±0.20, 19.60±0.20, 22.58±0.20, 26.19±0.20, and 27.07±0.20;
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane hydrochloride quarterhydrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 5.19±0.20, 12.96±0.20, 13.00±0.20, 14.88±0.20, 14.98±0.20, 15.61±0.20, 17.79±0.20, 18.26±0.20, 18.93±0.020, 20.02±0.20, 20.67±0.20, 20.86±0.20, 21.72±0.20, 22.38±0.20, 22.55±0.20, 24.09±0.20, and 26.10±0.20;
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane hydrochloride sesquihydrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 4.94±0.20, 9.93±0.20, 14.09±0.20, 14.90±0.20, 17.85±0.20, 19.92±0.20, 21.72±0.20, 22.43±0.20, 22.63±0.20, and 23.95±0.20;
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane dihydrogen citrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 7.98±0.20, 11.98±0.720, 12.45±0.20, 15.76±0.20, 16.00±0.20, 17.75±0.20, 18.79±0.20, 18.82±0.20, 20.59±0.20, 22.25±0.20, 22.61±0.20, 24.16±0.20, 24.79±0.20, 25.06±0.20, 26.21±0.20, and 29.43±0.20;
• or
• crystalline (4s)-4-(5-phenyl-1,3,4-thiadiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane monohydrogen citrate demonstrating at least one characteristic peak in the powder X-ray diffraction pattern at values of two theta of 9.37±0.20, 9.62±0.20, 10.30±0.20, 11.24±0.20, 12.18±0.20, 13.73±0.20, 15.55±0.20, 16.17±0.20, 16.37±0.20, 16.76±0.20, 18.35±0.20, 18.67±0.20, 18.89±0.20, 19.98±0.20, 20.48±0.20, 20.94±0.20, 21.54±0.20, and 22.02±0.20.