Intracellular calcium concentration increase inhibitors

1. A boron compound represented by the formula (I) or nontoxic salts thereof,

wherein R 1 is (1) a hydrogen atom;

(2) —(CH 2 ) n —NR 2 R 3 , wherein n represents an integer of 1 to 3, R 2 and R 3 each independently represent, a hydrogen atom, C1–4 alkyl, mono-cyclic C5–6 carboring, or C1–4 alkyl substituted with mono-cyclic C5–6 carboring, wherein the carbon atom of —(CH 2 ) n — may be substituted with 1 to 2 R 4 , and the carboring may be further substituted with 1 to 2 R 7 ,

R 4 is (a) C1–8 alkyl, (b) carboxyl, (c) C1–4 alkoxycarbonyl, (d) keto, (e) mono-cyclic C5–6 carboring, (f) guanidino(C1–2)alkyl, (g) C1–6 alkyl substituted with mono-cyclic C5–6 carboring, (h) C1–2 alkyl substituted with 4-chlorophenoxy, or (i) C1–4 alkyl substituted with di(C1–4 alkyl)amino;

(3) C1–6 alkyl or C2–6 alkenyl substituted with mono-cyclic C5–6 carboring, wherein the carboring may be substituted with 1 to 5 R 7 , and the C1–6 alkyl or C2–6 alkenyl may be further substituted with 1 to 2 R 10 ;

R 10 represents C1–4 alkyl or C2–4 alkenyl;

(4) —CHR 5 R 6 , wherein R 5 and R 6 independently represent

(i) mono-cyclic C5–6 carboring, or

(ii) C1–6 alkyl or C2–6 alkenyl substituted with mono-cyclic C5–6 carboring,

wherein the carboring may further be substituted with 1 to 5 R 7 ; or

R 7 represents (a) C1–4 alkyl, (b) C1–4 alkoxy, (c) a halogen atom, (d) —CF 3 , (e) nitro, (f) mono-cyclic C5–6 carboring, (g) C1–4 alkyl substituted with mono-cyclic C5–6 carboring, (h) amino, (i) —NHCO(C1–4 alkyl), or (j) C1–4 alkoxycarbonyl; G represents Cyc1;

Cyc1 represents mono- or bi-cyclic C5–10 carboring, wherein the carboring may be substituted with 1 to 5 R 8 ; Cyc2 represents mono- or bi-cyclic C5–10 carboring substituted with

wherein the carboring may be substituted with 1 to 4 R 9 ; Cyc3 and Cyc4 independently represents mono- or bi-cyclic C5–10 carboring which may be substituted with 1 to 2 R 7 ;

R 8 and R 9 independently represents

(a) C1–4 alkyl,

(b) C2–4 alkenyl,

(c) C1–4 alkoxy,

(d) a halogen atom,

(e) —CF 3 ,

(f) C1–4 alkylthio,

(g) amino,

(h) (C1–4 alkyl)amino,

(i) di(C1–4 alkyl)amino,

(j) formyl,

(k) phenyl,

(l) phenoxy,

(m) hydroxy(C1–2)alkyl,

(n) (mono- or bi-cyclic C5–10 carboring)-O—(C1–2)alkyl,

(o) C1–4 alkoxycarbonylvinyl,

(p) C1–2 alkyl substituted with a group selected from —O—(C1–2 alkylene)-phenyl, wherein phenyl may be substituted with 1 to 3 C1–4 alkoxy, —O—CONH-phenyl, wherein phenyl may be substituted with 1 to 3 C1–4 alkyl, nitro or C1–4 alkoxycarbonyl, or —O—CONH—(C1–4) alkyl, wherein alkyl may be substituted with 1 to 3 C1–4 alkyl, carboxyl or C1–4 alkoxycarbonyl,

(q) phenylthio,

(r) —CON(C1–4 alkyl) 2 ,

(s) —SO 2 N(C1–4 alkyl) 2 ,

(t) C1–4 alkoxy(C1–2)alkyl, or

(u) C1–4 alkoxycarbonyloxy(C1–2)alkyl,

in R 8 and R 9 , the carboring and phenyl may be substituted with 1 to 2 R 7 ;

p represents an integer of 1 to 4;

q represents an integer of 1 to 4; and

E represents a single bond.

2. A boron compound according to claim 1 , which is

(18) bis[2-(hydroxyphenylboryl)benzyl]ether,

(19) 1,4-bis(4-(hydroxyphenylboryl)phenoxy)butane,

(20) bis[4-(hydroxyphenylboryl)benzyl]butane,

(89) bis[2-[(2-aminoethoxy)phenylboryl]benzyl]ether,

(90) bis[4-[(2-aminoethoxy)phenylboryl]benzyl]ether,

(91) [4-[(2-aminoethoxy)phenylboryl]benzyl][2-[4-[(2-aminoethoxy)phenylboryl]phenyl]ethyl]ether, or

(92) [2-[(2-aminoethoxy)phenylboryl]benzyl][2-[4-[(2-aminoethoxy)phenylboryl]phenyl]ethyl]ether, or nontoxic salt thereof.

3. A composition comprising the boron compound of formula (I) according to claim 1 , or a nontoxic salt thereof and a pharmaceutically acceptable carrier.

4. A method for treatment of platelet aggregation, ischemic diseases in hearts and brains, allergosis, bronchial asthma, hypertension, cerebrovascular spasm, nephritis, pancreatitis comprising administering to a subject an effective amount of the boron compound of formula (I) according to claim 1 , or a nontoxic salt thereof.