Salts of quinuclidine derivative
There is provided an acid addition salt of (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate with an acid selected from the group consisting of (−)-(2S,3S)-tartaric acid, (+)-(2S,3S)-di-O-benzoyltartaric acid, (+)-(2S,3S)-di-O-(4-methylbenzoyl)tartaric acid, (−)-L-phenylalanine, benzenesulfonic acid, cyclohexanesulfamic acid, hydrobromic acid, naphthalene-2-sulfonic acid, sebacic acid, (+)-camphor-10-sulfonic acid, p-toluenesulfonic acid, ethanesulfonic acid, methanesulfonic acid and methyl phosphate, which has little hygroscopicity that affects the use as a drug or its drug substance, and is very useful as a drug or its drug substance.
1. An acid addition salt consisting of (−)-(3R)-quinuclidin-3-yl (1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate with an acid selected from the group consisting of (−)-(2S,3S)-tartaric acid, (+)-(2S,3S)-di-O-benzoyltartaric acid, (+)-(2S,3S)-di-O-(4-methylbenzoyl)tartaric acid, (−)-L-phenylalanine, benzenesulfonic acid, cyclohexanesulfamic acid, hydrobromic acid, naphthalene-2-sulfonic acid, sebacic acid, (+)-camphor-10-sulfonic acid, p-toluenesulfonic acid, ethanesulfonic acid, methanesulfonic acid and methyl phosphate.
2. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (−)-(2S,3S)-tartrate.
3. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (+)-(2S,3S)-di-O-benzoyltartrate.
4. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (+)-(2S,3S)-di-O-(4-methylbenzoyl)tartrate.
5. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (−)-L-phenylalaninate.
6. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate benzenesulfonate.
7. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate cyclohexanesulfamate.
8. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate hydrobromide.
9. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate naphthalene-2-sulfonate.
10. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate sebacate.
11. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (+)-camphor-10-sulfonate.
12. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate p-toluenesulfonate.
13. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate ethanesulfonate.
14. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate methanesulfonate.
15. The acid addition salt according to claim 1 , wherein the salt is (−)-(3R)-quinuclidin-3-yl(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate methyl phosphate.
16. A pharmaceutical composition comprising one or more compounds mentioned in claim 1 as an active ingredient.