Claims for Patent: 8,067,396

Summary for Patent: 8,067,396

Title:	Amino alcohol compounds or phosphonic acid derivatives thereof
Abstract:	A compound having a formula II(a): ##STR00001## wherein R.sup.1 and R.sup.2 are hydrogen lower alkyl, lower aliphatic acyl, or lower alkoxycarbonyl; R.sup.4 is C.sub.1-C.sub.4 alkyl; n is 2 or 3; X is a formula .dbd.N-D, wherein D is hydrogen, C.sub.1-C.sub.6 alkyl or phenyl; Y is ethylene, ethynylene, --CO--CH.sub.2--, --CH(OH)--CH.sub.2-- or phenylene; Z is C.sub.1-C.sub.6 alkylene; R.sup.5 is C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl; R.sup.6 and R.sup.7 are hydrogen, lower alkyl, halogeno lower alkyl, lower alkoxy or lower alkylthio; and R.sup.10 and R.sup.11 are hydrogen or lower alkyl.
Inventor(s):	Nishi; Takahide (Tokyo, JP), Shimozato; Takaichi (Miura, JP), Nara; Futoshi (Yachiyo, JP), Miyazaki; Shojiro (Tokyo, JP)
Assignee:	Sankyo Company, Limited (Tokyo, JP)
Application Number:	12/460,884
Patent Claims:	1. A compound having a formula II(a): ##STR00065## wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, or a lower alkoxycarbonyl group; R.sup.4 represents a C.sub.1-C.sub.4 alkyl group; n represents an integer 2 or 3; X represents a group of the formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.1-C.sub.6 alkyl group or a phenyl group; Y represents an ethylene group, an ethynylene group, a group of the formula --CO--CH.sub.2--, a group of a formula --CH(OH)--CH.sub.2--, an unsubstituted phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group; Z represents an unsubstituted C.sub.1-C.sub.6 alkylene group or a C.sub.1-C.sub.6 alkylene group substituted with from 1 to 3 hydroxyl groups; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected, from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower alkylthio group; R.sup.6 and R.sup.7 each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group or a lower alkylthio group; R.sup.10 and R.sup.11 are the same or different and each represents a hydrogen atom or a lower alkyl group; or a pharmacologically acceptable salt thereof. 2. The compound according to claim 1, wherein R.sup.2 are the same or different and each represents a hydrogen atom, a C.sub.1-C.sub.2 alkyl group, a C.sub.1-C.sub.2 aliphatic acyl group or a C.sub.6-C.sub.10 alkoxycarbonyl group; R.sup.4 represents a C.sub.1-C.sub.2 alkyl group; n represents an integer 2 or 3; X represents a group of the formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a phenyl group; Y represents an ethylene group, an ethynylene group, a group of the formula --CO--CH.sub.2--, a group of a formula --CH(OH)--CH.sub.2--, an unsubstituted phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group; Z represents an unsubstituted C.sub.1-C.sub.5 alkylene group or a C.sub.1-C.sub.5 alkylene group substituted with from 1 to 3 hydroxyl groups; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower alkylthio group; R.sup.6 and R.sup.7 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, or a lower alkylthio group; R.sup.10 and R.sup.11 are the same or different and each represents a hydrogen atom, a methyl group, or an ethyl group; or a pharmacologically acceptable salt thereof. 3. The compound according to claim 1, wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a methyl group, an acetyl group or a methoxycarbonyl group; R.sup.4 represents a methyl group; n represents an integer 2; X represents a group of formula .dbd.N--CH.sub.3; Y represents an ethylene group, an ethynylene group, a group of the formula --CO--CH.sub.2-- or a phenylene group; represents an unsubstituted ethylene group, an unsubstituted trimethylene group, an unsubstituted tetramethylene group, or an ethylene, trimethylene, or tetramethylene group substituted with one hydroxyl group; R.sup.5 represents an unsubstituted C.sub.1-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; R.sup.6 and R.sup.7 each represent a hydrogen atom; R.sup.10 and R.sup.11 each represent a hydrogen atom; or a pharmacologically acceptable salt thereof. 4. The compound according to claim 1, wherein R.sup.1 and R.sup.2 each represent a hydrogen atom; R.sup.4 represents a methyl group; n represents an integer 2; X represents a group of a formula: .dbd.N--CH.sub.3; Y represents a group of the formula --CO--CH.sub.2--; Z represents an ethylene group or a trimethylene group; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.5-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; R.sup.6 and R.sup.7 each represent a hydrogen atom; R.sup.10 and R.sup.11 each represent a hydrogen atom; or a pharmacologically acceptable salt thereof. 5. The compound according to claim 1, wherein said compound is selected from the group consisting of mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]-1-butyl phosphate, and mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}-1-b- utyl phosphate, or a pharmacologically acceptable salt thereof. 6. The compound according to claim 1, wherein said compound is selected from the group consisting of mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-y- l}-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]-1-- butyl phosphate, mono 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol- -2-yl}-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)-pyrrol-2-yl]-1-but- yl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}-1- -butyl phosphate, mono 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-(1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-(1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-y- l}-1-butyl phosphate and mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl}butanoyl]pyrrol-2-y- l}-1-butyl phosphate, or a pharmacologically acceptable salt thereof. 7. A compound having a formula (IIIa): ##STR00066## wherein R.sup.1 and R.sup.2 each represent a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, or a lower alkoxycarbonyl group; R.sup.4 represents a C.sub.1-C.sub.4 alkyl group; n represents an integer 2 or 3; X represents a group of the formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a phenyl group; Y represents an ethylene group, an ethynylene group, a group of the formula --CO--CH.sub.2--, a group of a formula --CH(OH)--CH.sub.2--, an unsubstituted phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group; Z represents an unsubstituted C.sub.1-C.sub.6 alkylene group or a C.sub.1-C.sub.6 alkylene group substituted with from 1 to 3 hydroxyl groups; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogen lower alkyl group, a lower alkoxy group and a lower alkylthio group; R.sup.6 and R.sup.7 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, or a lower alkylthio group; R.sup.10 and R.sup.11 are the same or different and each represents a hydrogen atom or a lower alkyl group; or a pharmacologically acceptable salt thereof. 8. The compound according to claim 7, wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a C.sub.1-C.sub.2 alkyl group, a C.sub.1-C.sub.2 aliphatic acyl group, or a alkoxycarbonyl group; R.sup.4 represents a C.sub.1-C.sub.2 alkyl group; n represents an integer 2 or 3; X represents a group of the formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a phenyl group; Y represents an ethylene group, an ethynylene group, a group of formula --CO--CH.sub.2--, a group of a formula --CH(OH)--CH.sub.2--, an unsubstituted phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group; Z represents an unsubstituted C.sub.1-C.sub.5 alkylene group or a C.sub.1-C.sub.5 alkylene group substituted with from 1 to 3 hydroxyl groups; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.1-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower alkylthio group; R.sup.6 and R.sup.7 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, or a lower alkylthio group; R.sup.10 and R.sup.11 are the same or different and each represents a hydrogen atom, a methyl group, or an ethyl group; or a pharmacologically acceptable salt thereof. 9. The compound according to claim 7, wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a methyl group, an acetyl group, or a methoxycarbonyl group; R.sup.4 represents a methyl group; n represents an integer 2; X represents a group of a formula .dbd.N--CH.sub.3; Y represents an ethylene group, an ethynylene group, a group of the formula --CO--CH.sub.2--, or a phenylene group; Z represents an unsubstituted ethylene group, an unsubstituted trimethylene group, an unsubstituted tetramethylene group, or an ethylene, trimethylene, or tetramethylene group substituted with one hydroxyl group; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, and a lower alkoxy group; R.sup.6 and R.sup.7 each represents a hydrogen atom; R.sup.10 and R.sup.11 each represents a hydrogen atom; or a pharmacologically acceptable salt thereof. 10. The compound according to claim 7, wherein R.sup.1 and R.sup.2 each represent a hydrogen atom; R.sup.4 represents a methyl group; n represents an integer 2; X represents a group of a formula .dbd.N--CH.sub.3; Y represents a group of the formula --CO--CH.sub.2--; Z represents an ethylene group or a trimethylene group; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; R.sup.6 and R.sup.7 each represent a hydrogen atom; R.sup.10 and R.sup.11 each represent a hydrogen atom; or a pharmacologically acceptable salt thereof. 11. The compound according to claim 7, wherein said compound is a compound selected from the group consisting of 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]pentylpho- sphonic acid, 3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-y- l}pentylphosphonic acid, 3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]pen- tylphosphonic acid, 3-amino-3-methyl-5-{1-methyl-5-[3-(4-dimethylphenoxy)prop-1-ynyl]pyrrol-2- -yl}pentylphosphonic acid, 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl) pyrrol-2-yl]pentylphosphonic acid, 3-amino-3 methyl-5-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic acid, 3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentyl- phosphonic acid, 3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylph- osphonic acid, 3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosph- onic acid, 3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-y- l]pentylphosphonic acid, 3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphospho- nic acid, and 3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylpho- sphonic acid, or a pharmacologically acceptable salt thereof. 12. A pharmaceutical composition comprising (i) a pharmaceutically effective amount of at least one immunosuppressant selected from the group consisting of cyclosporin A, tacrolimus, rapamycin, gusperimus, everolimus, tresperimus, anisperimus, SDZ-281-240, ABT-281, tigderimus, A-119435, 17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazinocarbonyloxy)- -3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetrameth- yl-11,28-dioxa-4-azatricyclo[22.3.4.0.sup.4,9]octacos-18-ene-2,3,10,16-tet- rone, leflunomide, methotrexate, remicade and enbrel; and (ii) a pharmaceutically effective amount of a compound having a formula (Ia): ##STR00067## wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a lower alkyl group, or a protecting group of the amino group; R.sup.3 represents a hydrogen atom, a lower alkyl group, or a protecting group of the hydroxyl group; R.sup.4 represents a lower alkyl group; n represents an integer of from 1 to 6; X represents an oxygen atom or a group of a formula .dbd.N-D wherein D represents a hydrogen atom, a C.sub.6-C.sub.10 aryl group, a lower alkylsulfonyl group, a C.sub.6-C.sub.10 arylsulfonyl group, or a group selected from Substituent group (a); Y represents an ethylene group, a vinylene group, an ethynylene group, a group of a formula -E-CH.sub.2--, wherein E represents a carbonyl group or a group of a formula --CH(OH)--, a C.sub.6-C.sub.10 arylene group, or a C.sub.6-C.sub.10 arylene group substituted with from 1 to 3 substituents selected from Substituent group (a); Z represents a single bond, an unsubstituted C.sub.1-C.sub.10 alkylene group, a C.sub.1-C.sub.10 alkylene group substituted with from 1 to 3 substituents selected from Substituent group (a) and Substituent group (b), C.sub.1-C.sub.10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C.sub.1-C.sub.10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain; R.sup.5 represents a hydrogen atom, an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, C.sub.3-C.sub.10 cycloalkyl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C.sub.1-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), or a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from Substituent group (a) and Substituent group (b); R.sup.6 and R.sup.7 are the same or different and each represents a hydrogen atom or a group selected from Substituent group (a); Substituent group (a) is selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a lower alkylthio group, a carboxyl group, a lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, an amino group, a mono-lower alkylamino group, a di-lower alkylamino group, a lower aliphatic acylamino group, a cyano group and a nitro group; and Substituent group (b) is selected from the group consisting of an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom, a C.sub.3-C.sub.10 cycloalkyl group substituted with from 1 to 3 substituents selected from Substituent group (a), a C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from Substituent group (a), and a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, in which said heterocyclic group is substituted with from 1 to 3 substituents selected from Substituent group (a); provided that when R.sup.5 represents a hydrogen atom, then Z represents a branched chain C.sub.1-C.sub.10 alkylene group, a C.sub.1-C.sub.10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C.sub.1-C.sub.10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C.sub.1-C.sub.10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 13. The pharmaceutical composition according to claim 12, wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a C.sub.1-C.sub.2 alkyl group, a C.sub.1-C.sub.2 aliphatic acyl group, or a C.sub.1-C.sub.2 alkoxycarbonyl group; R.sup.2 represents a hydrogen atom, a lower alkyl group or a lower aliphatic acyl group; R.sup.4 represents a C.sub.1-C.sub.2 alkyl group; n represents an integer 2 or 3; X represents a group of the formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a phenyl group; Y represents an ethylene group, an ethynylene group, a group of the formula --CO--CH.sub.2--, a group of a formula --CH(OH)--CH.sub.2--, an unsubstituted phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group; Z represents an unsubstituted C.sub.1-C.sub.5 alkylene group or a C.sub.1-C.sub.5 alkylene group substituted with from 1 to 3 hydroxyl groups; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.1-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower alkylthio group; R.sup.6 and R.sup.7 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, or a lower alkylthio group; or a pharmacologically acceptable salt thereof. 14. The pharmaceutical composition according to claim 12, wherein R.sup.1 and R.sup.2 each represent a hydrogen atom; R.sup.4 represents a methyl group; n represents an integer 2; X represents a group of a formula .dbd.N--CH.sub.3; Y represents a group of the formula --CO--CH.sub.2--; Z represents an ethylene group or a trimethylene group R.sup.5 represents an unsubstituted. C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, and a lower alkoxy group; R.sup.6 and R.sup.7 each represents a hydrogen atom; or a pharmacologically acceptable salt thereof. 15. The pharmaceutical composition according to claim 12, wherein the compound is selected from the group consisting of 2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}butan-1-ol, 2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}butan-1-ol- , 2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(4-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}butan-- 1-ol, 2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}- butan-1-ol, 2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan- -1-ol, 2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}- butan-1-ol, 2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan- -1-ol, 2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}- butan-1-ol, 2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}b- utan-1-ol, 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]- butan-1-ol, 2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}butan-- 1-ol, 2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}b- utan-1-ol, 2-amino-2-methyl-4-{5-(3-cyclohexylmethoxyprop-1-ynyl)thiophen-- 2-yl}butan-1-ol, 2-amino-2-methyl-4-{5-(4-benzyloxybut-1-ynyl)thiophen-2-yl}butan-1-ol, 2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}butan-1-- ol, 2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol, 2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol, 2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol, 2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}butan- -1-ol, 2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl- }butan-1-ol, 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}b- utan-1-ol, 2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-ynyl]thiophen- -2-yl}butan-1-ol, 2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}- butan-1-ol, 2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}- butan-1-ol, 2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan- -1-ol, and 2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-- 2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 16. The pharmaceutical composition according to claim 12, wherein the compound is selected from the group consisting of 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5 (5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol, 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]butan-1-ol, and 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}buta- n-1-ol, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 17. The pharmaceutical composition according to claim 12, wherein the compound is selected from the group consisting of 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butan-1-o- l, 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2- -yl}butan-1-ol, 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]but- an-1-ol, 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-yny- l]pyrrol-2-yl}butan-1-ol, 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol, 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylpentanoyl)pyrrol-2-yl]butan-1- -ol, 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-- ol, 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan- -1-ol, 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2- -yl}butan-1-ol, 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol, 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-- ol, 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol- , 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexyl]butanoyl)pyrrol-2-yl]butan-1- -ol, 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol- -2-yl}butan-1-ol, 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)]butanoyl]pyrrol-2-- yl}butan-1-ol, 2-amino-2-methyl-4-(1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrro- l-2-yl}butan-1-ol, 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrro- l-2-yl}butan-1-ol, 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl)pyrrol-2-yl}b- utan-1-ol, 2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)]butyl]pyrrol- -2-yl}butan-1-ol, 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}b- utan-1-ol, 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyr- rol-2-yl}butan-1-ol, and 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butyl]pyrrol-2- -yl}butan-1-ol, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 18. A pharmaceutical composition comprising (i) a pharmaceutically effective amount of at least one immunosuppressant selected from the group consisting of cyclosporin A, tacrolimus, rapamycin, gusperimus, everolimus, tresperimus, anisperimus, SDZ-281-240, ABT-281, tigderimus, A-119435, 17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazinocarbonyloxy)- -3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19 21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.4.0.sup.4,9]octacos-18-e- ne-2,3,10,16-tetrone, leflunomide, methotrexate, remicade and enbrel; and (ii) a pharmaceutically effective amount of a compound having a formula (IIa): ##STR00068## wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, or a lower alkoxycarbonyl group; R.sup.4 represents a C.sub.1-C.sub.4 alkyl group; n represents an integer 2 or 3; X represents a group of the formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.1-C.sub.6 alkyl group or a phenyl group; Y represents an ethylene group, an ethynylene group, a group of the formula --CO--CH.sub.2--, a group of a formula --CH(OH)--CH.sub.2--, an unsubstituted phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group; Z represents an unsubstituted C.sub.1-C.sub.6 alkylene group or a C.sub.1-C.sub.6 alkylene group substituted with from 1 to 3 hydroxyl groups; R.sup.6 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower alkylthio group; R.sup.6 and R.sup.7 each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group or a lower alkylthio group; R.sup.10 and R.sup.11 are the same or different and each represents a hydrogen atom or a lower alkyl group; or a pharmacologically acceptable salt thereof. 19. The pharmaceutical composition according to claim 18, wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a C.sub.1-C.sub.2 alkyl group, a C.sub.1-C.sub.2 aliphatic acyl group, or a C.sub.1-C.sub.2 alkoxycarbonyl group; R.sup.4 represents a C.sub.1-C.sub.2 alkyl group; n represents an integer 2 or 3; X represents a group of a formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a phenyl group; Y represents an ethylene group, an ethynylene group, a group of formula --CO--CH.sub.2--, a group of the formula --CH(OH)--CH.sub.2--, an unsubstituted phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting halogen atom and a lower alkyl group; Z represents an unsubstituted C.sub.1-C.sub.5 alkylene group or a C.sub.1-C.sub.5 alkylene group substituted with from 1 to 3 hydroxyl groups; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower alkylthio group; R.sup.6 and R.sup.7 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, or a lower alkylthio group; R.sup.10 and R.sup.11 are the same or different and each represents a hydrogen atom, a methyl group, or an ethyl group; or a pharmacologically acceptable salt thereof. 20. The pharmaceutical composition according to claim 18, wherein R.sup.1 and R.sup.2 each represents a hydrogen atom; R.sup.4 represents a methyl group; n represents an integer 2; X represents a group of a formula .dbd.N--CH.sub.3; Y represents a group of the formula --CO--CH.sub.2; Z represents an ethylene group or a trimethylene group; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; R.sup.6 and R.sup.7 each represents a hydrogen atom; R.sup.10 and R.sup.11 each represents a hydrogen atom; or a pharmacologically acceptable salt thereof. 21. The pharmaceutical composition according to claim 18, wherein the compound is selected from the group consisting of mono 2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}-1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}-1-but- yl phosphate, mono 2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}-1-bu- tyl phosphate, mono 2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-bu- tyl phosphate, mono 2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-but- yl phosphate, mono 2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl)-- 1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}-1-but- yl phosphate, mono 2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}-1-but- yl phosphate, mono 2-amino-2-methyl-4-[5-(3-cyclohexylmethoxy)prop-1-ynyl]thiophen-2-yl]-1-b- utyl phosphate, mono 2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-bu- tyl phosphate, mono 2-amino-2-methyl-4-(5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl]-1-bu- tyl phosphate, mono 2-amino-2-methyl-4-{5-[3]-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}- -1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}-1-- butyl phosphate, mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}- -1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxyl)prop-1-ynyl]thiophen-2-yl- }-1-butyl phosphate, mono 2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-bu- tyl phosphate, and mono 2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-bu- tyl phosphate, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 22. The pharmaceutical composition according to claim 18, wherein the compound is selected from the group consisting of mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]-1-butyl phosphate, and mono 2-amino-2-methyl-4-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}-1-buty- l phosphate, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 23. The pharmaceutical composition according to claim 18, wherein the compound is selected from the group consisting of mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-y- l}-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]-1-- butyl phosphate, mono 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol- -2-yl}-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-buty- l phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}-1- -butyl phosphate, mono 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-y- l}-1-butyl phosphate and mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl}butanoyl]pyrrol-2-y- l}-1-butyl phosphate, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 24. A pharmaceutical composition comprising (i) a pharmaceutically effective amount of at least one immunosuppressant selected from the group consisting of cyclosporin A, tacrolimus, rapamycin, gusperimus, everolimus, tresperimus, anisperimus, SDZ-281-240, ABT-281, tigderimus, A-119435, 17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazinocarbonyloxy)- -3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetrameth- yl-11,28-dioxa-4-azatricyclo22.3.4.0.sup.4,9]octacos-18-ene-2,3,10,16-tetr- one, leflunomide, methotrexate, remicade and enbrel; and (ii) a pharmaceutically effective amount of a compound having a formula (IIIa): ##STR00069## wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a lower alkyl group, or a protecting group of the amino group; R.sup.4 represents a lower alkyl group; n represents an integer of from 1 to 6; X represents an oxygen atom or a group of a formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.6-C.sub.10 aryl group, a lower alkylsulfonyl group, a C.sub.6-C.sub.10 arylsulfonyl group, or a group selected from Substituent group (a); Y represents an ethylene group, a vinylene group, an ethynylene group, a group of a formula -E-CH.sub.2--, wherein E represents a carbonyl group or a group of a formula --CH(OH)--, a C.sub.6-C.sub.10 arylene group, or a C.sub.6-C.sub.10 arylene group substituted with from 1 to 3 substituents selected from Substituent group (a); Z represents a single bond, an unsubstituted C.sub.1-C.sub.10 alkylene group, a C.sub.1-C.sub.10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C.sub.1-C.sub.10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C.sub.1-C.sub.10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain; R.sup.5 represents a hydrogen atom, an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, a C.sub.3-C.sub.10 cycloalkyl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C.sub.1-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), or a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, in which said heterocyclic group is substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b); R.sup.6 and R.sup.7 are the same or different and each represents a hydrogen atom or a group selected from Substituent group (a); R.sup.10 and R.sup.11 are the same or different and each represents a hydrogen atom or a protecting group of phosphoric acid; Substituent group (a) is selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a lower alkylthio group, a carboxyl group, a lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, an amino group, a mono-lower alkylamino group, a di-lower alkylamino group, a lower aliphatic acylamino group, a cyano group, and a nitro group; and Substituent group (b) is selected from the group consisting of an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, a C.sub.3-C.sub.10 cycloalkyl group substituted with from 1 to 3 substituents selected from Substituent group (a), a C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from Substituent group (a), and a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, in which said heterocyclic group is substituted with from 1 to 3 substituents selected from Substituent group (a); provided that when R.sup.5 represents a hydrogen atom, then Z represents a branched chain C.sub.1-C.sub.10 alkylene group, a C.sub.1-C.sub.10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C.sub.1-C.sub.10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C.sub.1-C.sub.10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) and has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 25. The pharmaceutical composition according to claim 24, wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, a C.sub.1-C.sub.2 alkyl group, a C.sub.1-C.sub.2 aliphatic acyl group, or a C.sub.1-C.sub.2 alkoxycarbonyl group; R.sup.4 represents a C.sub.1-C.sub.2 alkyl group; n represents an integer 2 or 3; X represents a group of a formula .dbd.N-D, wherein D represents a hydrogen atom, a C.sub.1-C.sub.4 alkyl group or a phenyl group; Y represents an ethylene group, an ethynylene group, a group of the formula --CO--CH.sub.2--, a group of a formula --CH(OH)--CH.sub.2--, an unsubstituted phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group; Z represents an unsubstituted C.sub.1-C.sub.5 alkylene group or a C.sub.1-C.sub.5 alkylene group substituted with from 1 to 3 hydroxyl groups; R.sup.5 represents an unsubstituted a C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower alkylthio group; R.sup.6 and R.sup.7 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, or a lower alkylthio group; R.sup.10 and R.sup.11 are the same or different and each represents a hydrogen atom, a methyl group, or an ethyl group; or a pharmacologically acceptable salt thereof. 26. The pharmaceutical composition according to claim 24, wherein R.sup.1 and R.sup.2 each represent a hydrogen atom; R.sup.4 represents a methyl group; n represents an integer 2; X represents a group of a formula .dbd.N--CH.sub.3; Y represents a group of the formula --CO--CH.sub.2; Z represents ethylene group or a trimethylene group; R.sup.5 represents an unsubstituted C.sub.3-C.sub.10 cycloalkyl group, an unsubstituted C.sub.6-C.sub.10 aryl group, or a C.sub.3-C.sub.10 cycloalkyl or C.sub.6-C.sub.10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; R.sup.6 and R.sup.7 each represents a hydrogen atom; R.sup.10 and R.sup.11 each represents a hydrogen atom; or a pharmacologically acceptable salt thereof. 27. The pharmaceutical composition according to claim 24, wherein the compound is selected from the group consisting of 3-amino-3-methyl-5-[5-(4-cyclohexylbutyl)thiophen-2-yl]pentylphosphonic acid, 3-amino-3-methyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosp- honic acid, 3-amino-3-methyl-5-[5-(5-phenylpentyl)thiophen-2-yl]pentylphosphonic acid, 3-amino-3-methyl-5-{5-(4-cyclohexyloxybutyl)thiophen-2-yl}pentylpho- sphonic acid, 3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}pentylphosp- honic acid, 3-amino-3-methyl-5-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}pentylphos- phonic acid, 3-amino-3-methyl-5-[5-(4-benzyloxybutyl)thiophen-2-yl]pentylphosphonic acid, 3-amino-3-methyl-5-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]pentylp- hosphonic acid, 3-amino-3-methyl-5-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]pentylphosphonic acid, 3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]pentyl- phosphonic acid, 3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]pentylphosphonic 3-amino-3-methyl-5-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}pentyl- phosphonic acid, 3-amino-3-methyl-5-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}penty- lphosphonic acid, 3-amino-3-methyl-5-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}penty- lphosphonic acid, 3-amino-3-methyl-5-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}pentyl- phosphonic acid, 3-amino-3-methyl-5-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}p- entylphosphonic acid, 3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]pentylphos- phonic acid, 3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}pentyl- phosphonic acid, 3-amino-3-methyl-5-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}pentyl- phosphonic acid, 3-amino-3-methyl-5-[5-(3-cyclohexylmethoxy)prop-1-ynyl]thiophen-2-yl]pent- ylphosphonic acid, 3-amino-3-methyl-5-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]pentylphosphon- ic acid, 3-amino-3-methyl-5-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]pentylp- hosphonic acid, 3-amino-3-methyl-5-[5-(4-phenylbutanoyl)thiophen-2-yl]pentylphosphonic acid, 3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylph- osphonic acid, 3-amino-3-methyl-5-[5-(5-phenylpentanoyl)thiophen-2-yl]pentylphosphonic acid, 3-amino-3-methyl-5-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}pe- ntylphosphonic acid, 3-amino-3-ethyl-5-{5-(5-cyclohexylpentyl)thiophen-2-yl}pentylphosphonic acid, 3-amino-3-ethyl-5-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]pentylp- hosphonic acid, 3-amino-3-ethyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphoni- c acid, 3-amino-3-methyl-5-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-y- l}pentylphosphonic acid, 3-amino-3-methyl-5-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}penty- lphosphonic acid, 3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}p- entylphosphonic acid, 3-amino-3-methyl-5-{5-[3-(3-methoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}pen- tylphosphonic acid, 3-amino-3-methyl-5-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}- pentylphosphonic acid, 3-amino-3-methyl-5-{5-[3-(3,5-dimethoxyphenoxyl)prop-1-ynyl]thiophen-2-yl- }pentylphosphonic acid, 3-amino-3-methyl-5-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}penty- lphosphonic acid, and 3-amino-3-methyl-5-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}penty- lphosphonic acid, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 28. The pharmaceutical composition according to claim 24, wherein the compound is selected from the group consisting of 3-amino-3-methyl-5-[5-(5-phenylpentyl)furan-2-yl]pentylphosphonic acid, 3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]pentylphosphoni- c acid, 3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)furan-2-yl]pentylphosph- onic acid, 3-amino-3-methyl-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]penty- lphosphonic acid, 3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)furan-2-yl]pentylphosphonic acid, and 3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan- -2-yl}pentylphosphonic acid, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 29. The pharmaceutical composition according to claim 24, wherein the compound is selected from the group consisting of 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]pentylpho- sphonic acid, 3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-y- l}pentylphosphonic acid, 3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]pen- tylphosphonic acid, 3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethy]phenoxy)prop-1-ynyl]pyrrol- -2-yl}pentylphosphonic acid, 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosp- honic acid, 3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylp- hosphonic acid, 3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosph- onic acid, 3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-y- l]pentylphosphonic acid, 3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosph- onic acid, 3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-y- l]pentylphosphonic acid, 3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphospho- nic acid, and 3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylpho- sphonic acid, or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof. 30. The pharmaceutical composition according to claim 12, 18 or 24, wherein the at least one immunosuppressant is selected from the group consisting of cyclosporin A, tacrolimus, rapamycin, leflunomide, methotrexate, remicade, and enbrel. 31. A method for the treatment of an autoimmune disease in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to claim 1 or 7. 32. A method for the treatment of rheumatoid arthritis in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to claim 1 or 7. 33. A method for the treatment of psoriasis in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according claim 1 or 7. 34. A method for the treatment of Crohn's disease or ulcerative colitis in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to claim 1 or 7. 35. A method for the treatment of multiple sclerosis in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to claim 1 or 7. 36. A method for the treatment of atopic dermatitis in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to claim 1 or 7. 37. A method for the treatment of insulin dependent diabetes mellitus in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to claim 1 or 7. 38. A method for the treatment of glomerular nephritis in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to claim 1 or 7. 39. A method for the treatment of rejection caused by transplantation of an organ or skin in a human in need thereof which comprises administering to said human a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt or a pharmacologically acceptable ester according to claim 1 or 7. 40. A method for the treatment of an autoimmune disease in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according to claim 12, 18 or 24. 41. A method for the treatment of rheumatoid arthritis in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according claim 12, 18 or 24. 42. A method for the treatment of psoriasis in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according to claim 12, 18 or 24. 43. A method for the treatment of Crohn's disease or ulcerative colitis in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according to 12, 18 or 24. 44. A method for the treatment of multiple sclerosis in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according to claim 12, 18 or 24. 45. A method for the treatment of atopic dermatitis in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according to claim 12, 18 or 24. 46. A method for the treatment of insulin dependent diabetes mellitus in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according to claim 12, 18 or 24. 47. A method for the treatment of glomerular nephritis in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according to claim 12, 18 or 24. 48. A method for the treatment of rejection caused by transplantation of an organ or skin in a human which comprises administering to said human a pharmaceutically effective amount of a pharmaceutical composition according to claim 12, 18 or 24. 49. The compound according to claim 1, wherein the compound is mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate. 50. The compound according to claim 1, wherein the compound is mono 2-amino-2-methyl-{1-methyl-5-[4-(4-methylphenyl)butanoyl)pyrrol-2-yl]-1-b- utyl phosphate. 51. The compound according to claim 1, wherein the compound is mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl)pyrrol-2-y- l]-1-butyl phosphate. 52. The compound according to claim 7, wherein the compound is 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosp- honic acid. 53. The pharmaceutical composition according to claim 12, wherein the immunosuppressant is cyclosporin A. 54. The pharmaceutical composition according to claim 12, wherein the immunosuppressant is tacrolimus. 55. The pharmaceutical composition according to claim 18, wherein the immunosuppressant is cyclosporin A. 56. The pharmaceutical composition according to claim 18, wherein the immunosuppressant is tacrolimus. 57. The pharmaceutical composition according to claim 24, wherein the immunosuppressant is cyclosporin A. 58. The pharmaceutical composition according to claim 24, wherein the immunosuppressant is tacrolimus.

Details for Patent 8,067,396

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2022-01-11
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2022-01-11
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2022-01-11
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2022-01-11
Immunex Corporation	ENBREL	etanercept	Injection	103795	02/01/2007		2022-01-11
Immunex Corporation	ENBREL MINI	etanercept	Injection	103795	09/14/2017		2022-01-11