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AssigneeOno Pharmaceutical Co., Ltd.
InventorsYoshikazu Takaoka, Masaki Okamoto, Yuuichi Genba
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The present invention relates to a new crystal of triazaspiro[5.5]undecane derivatives. The crystal of a non-solvate of (3R)-1-butyl-2,5-dioxo-3-[(1R)-1-hydroxy-1-cyclohexylmethyl]-9-[4-(4-carboxyphenyloxy)phenylmethyl]-1,4,9-triazaspiro[5.5]undecane hydrochloride have safety as drug substance, and have possibility to supply at large scale. And the crystal have an antagonistic activity against the interaction between chemokine and chemokine receptor, therefore, it is useful for manufacture of an agent for treating and/or preventing diseases such as various inflammatory diseases, asthma, atopic dermatitis, nettle rash, allergy disease, nephritis, nephropathy, hepatitis, arthritis, chronic rheumatoid arthritis, autoimmune disease, transplanted organ rejection reactions, acquired immunodeficiency syndrome and the like.
A crystal of (3R)-1-butyl-2,5-dioxo-3-[(1R)-1-hydroxy-1-cyclohexylmethyl]-9-[4-(4-carboxyphenyloxy)phenylmethyl]-1,4,9-triazaspiro[5.5]undecane hydrochloride.
A process for producing a crystal of a non-solvate of (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride, which comprises carrying out crystallization from a lower alcohol solvent which may contain water or a water-miscible ether solvent which may contain water, in which a crudely purified substance of (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride is dissolved or suspended.
A process for producing a crystal of a non-solvate of (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride, which comprises:
A process for producing a crystal of a non-solvate of (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride, which comprises dissolving or suspending a solvate of (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride or amorphous (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride in C1-4 alkyl acetate, followed by heating at about 40° C. to about 80° C.;
(canceled)
Dependencies are inferred from the claim text.