Triaryl methane compounds and their use in the treatment of diarrhea and scours
AssigneesBeth Israel Deaconess Medical Center, Inc., Children's Medical Center Corporation
InventorsWayne I. Lencer, Carlo Brugnara, Seth Alper
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Abstract
A method and product for treating and preventing diarrhea and scours is provided. The method involves treating a subject who has diarrhea, or scours, or is at risk of getting diarrhea or scours with an aromatic compound of the invention. The products of the invention are a veterinary preparation of the aromatic compound of the invention and an anti-scours agent, and a pharmaceutical preparation of the aromatic compound of the invention and an anti-diarrheal agent.
Claims14
A method for treating diarrhea, comprising, administering an effective amount for inhibiting Cl− secretion of an aromatic compound to a subject, wherein the aromatic compound has the general formula:
- or a pharmaceutically acceptable salt or hydrate thereof, wherein:
- n is 0, 1, 2, 3 or 4;
- p is 0 or 1;
- X is absent, (C1-C3)alkyl, (C1-C3)alkenyl, (C1-C3)alkynyl, SCH2, OCH2, or NOCH2;
- Y is C, N, P, Si or Ge;
- R′ is -halo, —R, —OR, —SR, —NR2, —ONR2, —NO2, —CN, —C(O)R, —C(S)R, —C(O)OR, —C(S)OR, —C(O)SR, —C(S)SR, —C(O)NR2, —C(S)NR2, —C(O)NR(OR), —C(S)NR(OR), —C(O)NR(SR), C(S)NR(SR), —CH(CN)2, —CH[C(O)R]2, —CH[C(S)R]2, —CH[C(O)OR]2, —CH[C(S)OR]2, —CH[C(O)SR]2, —CH aryl, or heteroaryl;
- Ar1 is aryl, substituted aryl, heteroaryl, (C5-C8)cycloalkyl or (C5-C8)heterocycloalkyl;
- Ar2 is aryl or substituted aryl;
- Ar3 is aryl, substituted aryl, biaryl, biphenyl, bibenzyl, or heteroaryl other than imidazole, nitroimidazole and triazole;
- each R is independently selected from the group consisting of —H, (C1-C6)alkyl, substituted (C1-C6)alkyl, (C1-C6)alkenyl, substituted (C1-C6)alkenyl(C1-C6)alkynyl, substituted (C1-C6)alkynyl, and (C1-C6)alkoxy;
- the aryl substituents are each independently selected from the group consisting of -halo, trihalomethyl, —R, —R1, —OR1, —SR1, NR12, —NO2, —CN, —C(O)R1, —C(S)R1, —C(O)OR1, —C(S)OR1, —C(O)SR, and —C(S)SR1;
- the alkyl, alkenyl and alkynyl substituents are each independently selected from the group consisting of -halo, —R1, —OR1, —SR1, N(R1)2, —NO2, —CN, —C(O)R12, —C(S)R1, —C(O)OR1, —C(S)OR1, —C(O)SR1, —C(S)SR1, aryl, γ-butyrolactonyl, pyrrolidinyl and succinic anhydridyl;
- and each R1 is independently selected from the group consisting of —H, (C1-C6)alkyl, (C1-C6)alkenyl and (C1-C6)alkynyl, and
- provided that neither Ar1 nor Ar3 are oxadiazolyl when X is absent, Y is C, p=O, n=1-4, and R′=NR2.
A method for treating scours, the method comprising the step of:
- administering to a subject in need of such treatment, an aromatic compound in an amount effective to inhibit scours, wherein the aromatic compound has the general formula:
- or a pharmaceutically acceptable salt or hydrate thereof, wherein:
- n is 0, 1, 2, 3 or 4;
- p is 0 or 1;
- X is absent, (C1-C3)alkyl, (C1-C3)alkenyl, (C1-C3)alkynyl, SCH2, OCH2, or NOCH2;
- Y is C, N, P, Si or Ge;
- R′ is -halo, —R, —OR, —SR, —NR2, —ONR2, —NO2, —CN, —C(O)R, —C(S)R, —C(O)OR, —C(S)OR, —C(O)SR, —C(S)SR, —C(O)NR2, —C(S)NR2, —C(O)NR(OR), —C(S)NR(OR), —C(O)NR(SR), C(S)NR(SR), —CH(CN)2, —CH[C(O)R]2, —CH[C(S)R]2, —CH[C(O)OR]2, —CH[C(S)OR]2, —CH[C(O)SR]2, —CH[C(S)SR]2, aryl, or heteroaryl;
- Ar1 is aryl, substituted aryl, heteroaryl, (C5-C8)cycloalkyl or (C5-C8)heterocycloalkyl;
- Ar2 is aryl or substituted aryl;
- Ar3 is aryl, substituted aryl, biaryl, biphenyl, bibenzyl, or heteroaryl other than imidazole, nitroimidazole and triazole;
- each R is independently selected from the group consisting of —H, (C1-C6)alkyl, substituted (C1-C6)alkyl, (C1-C6)alkenyl, substituted (C1-C6)alkenyl(C1-C6)alkynyl, substituted (C1-C6)alkynyl, and (C1-C6)alkoxy;
- the aryl substituents are each independently selected from the group consisting of -halo, trihalomethyl, —R, —R1, —OR1, —SR1, NR12, —NO2, —CN, —C(O)R1, —C(S)R1, —C(O)OR1, —C(S)OR1, —C(O)SR1 and —C(S)SR1;
- the alkyl, alkenyl and alkynyl substituents are each independently selected from the group consisting of -halo, —R1, —OR1, —SR1, N(R1)2, —NO2, —CN, —C(O)R1, —C(S)R1, —C(O)OR1, —C(S)OR1, —C(O)SR1, —C(S)SR1, aryl, γ-butyrolactonyl, pyrrolidinyl and succinic anhydridyl;
- and each R1 is independently selected from the group consisting of —H, (C1-C6)alkyl, (C1-C6)alkenyl and (C1-C6)alkynyl, and
- provided that neither Ar1 nor Ar3 are oxadiazolyl when X is absent, Y is C, p=0, n=1-4, and R′=NR2.
Dependencies are inferred from the claim text.