Provided is a series of homologous small molecule immune agonists and novel bifunctional immune targeting compounds having targeting and immune activation functions, which are obtained by coupling the small molecule immune agonists to targeting drugs. The resulting immune targeting compounds are beneficial for enhancing immune activation effects, and anti-tumor and other disease fighting effects of the targeting drug. The enhanced effect is produced from a synergy of immunological anti-tumor factors (such as IFN-γ) and inhibition at pathogenic targeting sites.

Provided is a series of homologous small molecule immune agonists and novel bifunctional immune targeting compounds having targeting and immune activation functions, which are obtained by coupling the small molecule immune agonists to targeting drugs. The resulting immune targeting compounds are beneficial for enhancing immune activation effects, and anti-tumor and other disease fighting effects of the targeting drug. The enhanced effect is produced from a synergy of immunological anti-tumor factors (such as IFN-γ) and inhibition at pathogenic targeting sites.

Provided are a novel compound having an antagonistic activity for the P2X.sub.7 receptor, and a pharmaceutical composition having an antagonistic activity for the P2X.sub.7 receptor. A compound represented by Formula (I): ##STR00001##
wherein Z.sup.1 is C(R.sup.4) or the like; R.sup.4 is a hydrogen atom or the like; Z.sup.2 is C(R.sup.5a)(R.sup.5a′) or the like; the dashed line represents the presence or absence of a bond; when the dashed line represents the presence of a bond, then R.sup.5a′ is absent; R.sup.5a and R.sup.5a′ are each independently a hydrogen atom or the like; Ring Q is a substituted or unsubstituted 5-membered non-aromatic heterocycle or the like; Y.sup.1 is O or the like; R.sup.2a is a group represented by the formula: —(C(R.sup.2a′)(R.sup.2b′)).sub.n—R.sup.1; R.sup.2b is a hydrogen atom or the like; R.sup.2a′ and R.sup.2b′ is each independently a hydrogen atom or the like; R.sup.1 is substituted or unsubstituted aromatic carbocyclyl or the like; X is N(R.sup.7a) or the like; R.sup.7a is a hydrogen atom or the like; R.sup.3 is substituted or unsubstituted aromatic carbocyclyl or the like; n is an integer from 0 to 4; and m is an integer from 0 to 4, or a pharmaceutically acceptable salt thereof.

Provided are a novel compound having an antagonistic activity for the P2X.sub.7 receptor, and a pharmaceutical composition having an antagonistic activity for the P2X.sub.7 receptor. A compound represented by Formula (I): ##STR00001##
wherein Z.sup.1 is C(R.sup.4) or the like; R.sup.4 is a hydrogen atom or the like; Z.sup.2 is C(R.sup.5a)(R.sup.5a′) or the like; the dashed line represents the presence or absence of a bond; when the dashed line represents the presence of a bond, then R.sup.5a′ is absent; R.sup.5a and R.sup.5a′ are each independently a hydrogen atom or the like; Ring Q is a substituted or unsubstituted 5-membered non-aromatic heterocycle or the like; Y.sup.1 is O or the like; R.sup.2a is a group represented by the formula: —(C(R.sup.2a′)(R.sup.2b′)).sub.n—R.sup.1; R.sup.2b is a hydrogen atom or the like; R.sup.2a′ and R.sup.2b′ is each independently a hydrogen atom or the like; R.sup.1 is substituted or unsubstituted aromatic carbocyclyl or the like; X is N(R.sup.7a) or the like; R.sup.7a is a hydrogen atom or the like; R.sup.3 is substituted or unsubstituted aromatic carbocyclyl or the like; n is an integer from 0 to 4; and m is an integer from 0 to 4, or a pharmaceutically acceptable salt thereof.

The present invention relates to compounds of Formula (I) or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula (I) for the treatment of cystic fibrosis. The invention also relates to a process for manufacturing compounds of Formula (I).

##STR00001##

The present invention relates to compounds of Formula (I) or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula (I) for the treatment of cystic fibrosis. The invention also relates to a process for manufacturing compounds of Formula (I).

##STR00001##

A compound of formula (I), for use in the treatment of non-traumatic acquired brain injury,

##STR00001## in which M represents a NR.sup.1R.sup.2 group, an OR.sup.1 group or a SR.sup.1 group, A represents a NR.sup.4R.sup.5 group, an OR.sup.10 group or a hydrogen atom, R.sup.3 is a (C.sub.1-C.sub.6)alkyl group, a (C.sub.1-C.sub.6)cycloalkyl group, an aryl group, a —CH.sub.2-aryl group, a CH.sub.2-(C.sub.1-C.sub.6)cycloalkyl group or a —CH.sub.2-heteroaryl group, and its addition salts with pharmaceutically acceptable acids. A compound of formula (I) wherein R.sup.5 is a (C.sub.1-C.sub.8)alkyl group or a (C.sub.1-C.sub.6)cycloalkyl group, said alkyl and cycloalkyl group being substituted with one, two or three —OCOR.sup.a group(s).

As a drug substance, a crystal having good physical properties is preferable. However, the crystal form that is most excellent as a drug substance may vary with the compound. In general, it is difficult to predict a crystal form of a drug substance having good physical properties, and it is required to variously examine each compound. Therefore, an object of the present invention is to provide a crystal having good physical properties as a drug substance for a novel compound.

The present invention relates to a crystal of the compound represented by the following formula (I) useful for the treatment of an inflammatory bowel disease.

##STR00001##

As a drug substance, a crystal having good physical properties is preferable. However, the crystal form that is most excellent as a drug substance may vary with the compound. In general, it is difficult to predict a crystal form of a drug substance having good physical properties, and it is required to variously examine each compound. Therefore, an object of the present invention is to provide a crystal having good physical properties as a drug substance for a novel compound.

The present invention relates to a crystal of the compound represented by the following formula (I) useful for the treatment of an inflammatory bowel disease.

##STR00001##

The disclosure provides for novel antimicrobial agents, methods of making, and methods of use thereof.