CA2436526A1 - Heterocyclic sulfonamide inhibitors of beta amyloid production - Google Patents

Heterocyclic sulfonamide inhibitors of beta amyloid production Download PDF

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Publication number
CA2436526A1
CA2436526A1 CA002436526A CA2436526A CA2436526A1 CA 2436526 A1 CA2436526 A1 CA 2436526A1 CA 002436526 A CA002436526 A CA 002436526A CA 2436526 A CA2436526 A CA 2436526A CA 2436526 A1 CA2436526 A1 CA 2436526A1
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sulfonamide
thiophene
substituted
chloro
hydroxymethyl
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CA002436526A
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CA2436526C (en
Inventor
Anthony Frank Kreft
Derek Cecil Cole
Kevin Roger Woller
Joseph Raymond Stock
George Diamantidis
Dennis Michael Kubrak
Kristina Martha Kutterer
William Jay Moore
David Scott Casebier
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Wyeth LLC
Arqule Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/64—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/34—Sulfur atoms

Abstract

Compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, T, W, X, Y and Z a re as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are described.

Claims (31)

1. A compound of Formula (I), or pharmaceutically acceptable salt thereof, wherein Formula (I) has the structure:

wherein:
R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, and (CH2)n(1,3)dioxane, where n is 2 to 5;
R3 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkylcycloalkyl, substituted alkylcycloalkyl, phenyl(substituted)alkyl, alkylOH, substituted alkylOH, alkylOBn, substituted alkylOBn, alkylpyridyl, substituted alkylpyridyl, alkylfuranyl, substituted alkylfuranyl, CH(OH)phenyl, CH(OH)substituted phenyl, alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl, N-substituted-piperidinyl, piperidinyl, substituted piperidinyl, tetrahydrothiopyran, substituted tetrahydrothiopyran, 2-indane, substituted 2-indane, phenyl, substituted phenyl, alkylNHR7, and substituted alkylNHR7;
with the proviso that R3 and R4 are not both hydrogen;
R7 is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, benzyl, substituted benzyl, alkylOH, substituted alkylOH, alkylSR8, or substituted alkylSR8;
R8 is alkyl, substituted alkyl, benzyl, or substituted benzyl;
or R3 and R4 may be joined to form a ring;

R5 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, CH2cycloalkyl, substituted CH2cycloalkyl, benzyl, substituted benzyl, and CH2CH2QR9;
Q is O, NH or S;
R9 is lower alkyl, substituted lower alkyl, phenyl, or substituted phenyl;
R6 is selected from the group consisting of hydrogen, halogen and CF3;
T is selected from the group consisting of W, Y and Z are independently selected from the group consisting of C, CR10 and N;
R10 is selected from the group consisting of hydrogen and halogen, with the proviso that at least one of W, Y and Z must be C;
X is selected from the group consisting of O, S, SO2, and NR11;
R11 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, benzyl, substituted benzyl, phenyl, and substituted phenyl;
provided that when the compound contains one or more chiral centers, at least one of the chiral centers must be of S-stereochemistry.
2. A compound of Formula (I), or pharmaceutically acceptable salt thereof, wherein Formula (I) has the structure:

wherein:
R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, and (CH2)n(1,3)dioxane, where n is 2 to 5;
R3 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkylcycloalkyl, substituted alkylcycloalkyl, phenyl(substituted)alkyl, alkylOH, substituted alkylOH, alkylOBn, substituted alkylOBn, alkylpyridyl, substituted alkylpyridyl, alkylfuranyl, substituted alkylfuranyl, CH(OH)phenyl, CH(OH)substituted phenyl, alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl, N-substituted-piperidinyl, piperidinyl, substituted piperidinyl, tetrahydrothiopyran, substituted tetrahydrothiopyran, 2-indane, substituted 2-indane, phenyl, substituted phenyl, alkylNHR7, and substituted alkylNHR7;
with the proviso that R3 and R4 are not both hydrogen;
R7 is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, benzyl, substituted benzyl, alkylOH, substituted alkylOH, alkylSR8, or substituted alkylSR8;
R8 is alkyl, substituted alkyl, benzyl, or substituted benzyl;
or R3 and R4 may be joined to form a ring;
R5 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, CH2cycloalkyl, substituted CH2cycloalkyl, benzyl, substituted benzyl, and CH2CH2QR9;
Q is O, NH or S;
R9 is lower alkyl, substituted lower alkyl, phenyl, or substituted phenyl;
R6 is selected from the group consisting of hydrogen, halogen and CF3;
T is W is C, wherein W provides the point of attachment to the SO2 group;
X is S;
Y and Z are independently C or CR10;
R10 is selected from the group consisting of hydrogen and halogen;
provided that when the compound contains one or more chiral centers, at least one of the chiral centers must be of S-stereochemistry.
3. A compound of Formula (I), or pharmaceutically acceptable salt thereof, wherein Formula (I) has the structure:

wherein:
R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, and (CH2)n(1,3)dioxane, where n is 2 to 5;
R3 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkylcycloalkyl, substituted alkylcycloalkyl, phenyl(substituted)alkyl, alkylOH, substituted alkylOH, alkylOBn, substituted alkylOBn, alkylpyridyl, substituted alkylpyridyl, alkylfuranyl, substituted alkylfuranyl, CH(OH)phenyl, CH(OH)substituted phenyl, alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl, N-substituted-piperidinyl, piperidinyl, substituted piperidinyl, tetrahydrothiopyran, substituted tetrahydrothiopyran, 2-indane, substituted 2-indane, phenyl, substituted phenyl, alkylNHR7, and substituted alkylNHR7;
with the proviso that R3 and R4 are not both hydrogen;

R7 is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, benzyl, substituted benzyl, alkylOH, substituted alkylOH, alkylSR8, or substituted alkylSR8;
R8 is alkyl, substituted alkyl, benzyl, or substituted benzyl;
or R3 and R4 may be joined to form a ring;
R5 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, CH2cycloalkyl, substituted CH2cycloalkyl, benzyl, substituted benzyl, and CH2CH2QR9;
Q is O, NH or S;
R9 is lower alkyl, substituted lower alkyl, phenyl, or substituted phenyl;
R6 is halogen;
T is W is C, wherein W provides the point of attachment to the SO2 group;
X is S;
Y and Z are independently C or CR10;
R10 is selected from the group consisting of hydrogen and halogen;
provided that when the compound contains one or more chiral centers, at least one of the chiral centers must be of S-stereochemistry.
4. A compound of Formula (I), or pharmaceutically acceptable salt thereof, wherein Formula (I) has the structure:

wherein:

R1 and R2 are hydrogen;
R3 is hydrogen;
R4 is a lower alkyl of S-stereochemistry;
R5 is hydrogen;
R6 is halogen;
T is X is S;
W, Y and Z are C, wherein W provides the point of attachment to the SO2 group.
5. A compound of Formula (I), or pharmaceutically acceptable salt thereof, wherein Formula (I) has the structure:

wherein:
R1 and R2 are hydrogen;
R3 is hydrogen;
R4 is a lower alkyl of S-stereochemistry;
R5 is hydrogen;
R6 is hydrogen or halogen;
T is X is O;
W, Y and Z are C, wherein W provides the point of attachment to the SO2 group.
6. A compound of Formula (I), or pharmaceutically acceptable salt thereof, wherein Formula (I) has the structure:

wherein:
R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, and (CH2)n(1,3)dioxane, where n is 2 to 5;
R3 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkylcycloalkyl, substituted alkylcycloalkyl, phenyl(substituted)alkyl, alkylOH, substituted alkylOH, alkylOBn, substituted alkylOBn, alkylpyridyl, substituted alkylpyridyl, alkylfuranyl, substituted alkylfuranyl, CH(OH)phenyl, CH(OH)substituted phenyl, alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl, N-substituted-piperidinyl, piperidinyl, substituted piperidinyl, tetrahydrothiopyran, substituted tetrahydrothiopyran, 2-indane, substituted 2-indane, phenyl, substituted phenyl, alkylNHR7, and substituted alkylNHR7;
with the proviso that R3 and R4 are not both hydrogen;
R7 is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, benzyl, substituted benzyl, alkylOH, substituted alkylOH, alkylSR8, or substituted alkylSR8;
R8 is alkyl, substituted alkyl, benzyl, or substituted benzyl;

or R3 and R4 may be joined to form a ring;
R5 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, CH2cycloalkyl, substituted CH2cycloalkyl, benzyl, substituted benzyl, and CH2CH2QR9;
Q is O, NH or S;
R9 is lower alkyl, substituted lower alkyl, phenyl, or substituted phenyl;
R6 is selected from the group consisting of hydrogen, halogen and CF3;
T is W, Y and Z are independently selected from the group consisting of C, CR10 and N;
R10 is selected from the group consisting of hydrogen and halogen, with the proviso that at least one of W, Y and Z must be C;
X is selected from the group consisting of O, S, SO2, and NR11;
R11 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, benzyl, substituted benzyl, phenyl, and substituted phenyl;
provided that when the compound contains one or more chiral centers, at least one of the chiral centers must be of S-stereochemistry.
7. A compound of Formula (I), or pharmaceutically acceptable salt thereof, wherein Formula (I) has the structure:

wherein:

R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, and (CH2)n(1,3)dioxane, where n is 2 to 5;
R3 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkylcycloalkyl, substituted alkylcycloalkyl, phenyl(substituted)alkyl, alkylOH, substituted alkylOH, alkylOBn, substituted alkylOBn, alkylpyridyl, substituted alkylpyridyl, alkylfuranyl, substituted alkylfuranyl, CH(OH)phenyl, CH(OH)substituted phenyl, alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl, N-substituted-piperidinyl, piperidinyl, substituted piperidinyl, tetrahydrothiopyran, substituted tetrahydrothiopyran, 2-indane, substituted 2-indane, phenyl, substituted phenyl, alkylNHR7, and substituted alkylNHR7;
with the proviso that R3 and R4 are not both hydrogen;
R7 is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, benzyl, substituted benzyl, alkylOH, substituted alkylOH, alkylSR8, or substituted alkylSR8;
R8 is alkyl, substituted alkyl, benzyl, or substituted benzyl;
or R3 and R4 may be joined to form a ring;
R5 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, CH2cycloalkyl, benzyl, substituted benzyl, and CH2CH2QR9;
Q is O, NH or S;
R9 is lower alkyl, substituted lower allyl, phenyl, or substituted phenyl;
R6 is selected from the group consisting of hydrogen, halogen and CF3;
T is W, Y and Z are independently selected from the group consisting of C, CR10 and N;

R10 is selected from the group consisting of hydrogen and halogen, with the proviso that at least one of W, Y and Z must be C;
X is selected from the group consisting of O, S, SO2, and NR11;
R11 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, benzyl, substituted benzyl, phenyl, and substituted phenyl;
provided that when the compound contains one or more chiral centers, at least one of the chiral centers must be of S-stereochemistry.
8. The compound according to any of claims 1, 2, or 5 to 7, wherein R6 is halogen.
9. The compound according to any of claims 1 to 8, wherein R6 is chlorine or bromine.
10. The compound according to any of claims 1 to 3, wherein T is C(OH)R1R2 and R1 and R2 are each hydrogen.
11. The compound according to any of claims 1 to 7, wherein W and Z are both C.
12. The compound according to any of claims 1 to 3, 6 or 7, wherein R4 is lower alkyl of S-stereochemistry.
13. The compound according to any of claims 1 to 3 or 5 to 7, wherein X
is S, W is C, Z is C, R6 is halogen, R4 is lower alkyl of S-stereochemistry, R3 is hydrogen, R5 is hydrogen, and R1 and R2 are each hydrogen.
14. The compound according to any of claims 1 to 3, 6, or 7, wherein R3CR4 is cyclohexyl.
15. The compound according to any of claims 1 to 3, 6, or 7, wherein R3CR4 is piperidine or N-substituted piperidine.
16. The compound according to any of claims 1 to 3, 6, or 7, wherein X is S, and W, Y and Z are independently C or CR10.
17. The compound according to claim 1, wherein the compound is selected from the group consisting of:
3-bromo-5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
4-bromo-5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
2,5-dichloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-3-sulfonamide;
4,5-dichloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]thiophene-2-sulfonamide;
5-bromo-N-[(1R)-1-(hydroxymethyl)-2-methylpropyl]thiophene-2-sulfonamide;
4,5-dibromo-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S)-1-cyclohexyl-2-hydroxyethyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S)-1-cyclohexyl-2-hydroxyethyl]thiophene-2-sulfonamide;

5-chloro-N-[1-(hydroxymethyl)-2-phenylpropyl]thiophene-2-sulfonamide;
5-bromo-N-[1-(hydroxymethyl)-2-phenylpropyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide 1,1-dioxide;
5-chloro-N-[1-(hydroxymethyl)-2,3-dimethylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[1-(hydroxymethyl)-2-methylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[2-ethyl-1-(hydroxymethyl)hexyl]thiophene-2-sulfonamide;
5-chloro-N-[2-hydroxy-1-(2,4,6-trimethylcyclohex-3-en-1-yl)ethyl]thiophene2-sulfonamide;
5-chloro-N-(1-cyclohex-3-en-1-yl-2-hydroxyethyl)thiophene-2-sulfonamide;
5-chloro-N-(1-cyclopentyl-2-hydroxyethyl)thiophene-2-sulfonamide;
5-bromo-N-[(1S)-1-(hydroxymethyl)-1,2-dimethylpropyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S)-1-(hydroxymethyl)-1,2-dimethylpropyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2,4-dimethylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-(4-methoxyphenyl)propyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-methyloctyl]thiophene-2-sulfonamide;

5-chloro-N-[(1S)-2-ethyl-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-2-ethyl-1-(hydroxymethyl)-4-methylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-(4-methoxyphenyl)butyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2S)-2-ethyl-1-(hydroxymethyl)pentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-4-methyl-2-propylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-(4-methoxyphenyl)pentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-propyloctyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-phenylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylheptyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S)-2-propyl-1-(hydroxymethyl)pentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2S)-2-ethyl-1-(hydroxymethyl)heptyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-isobutylheptyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-(4-methoxyphenyl)heptyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-pentyloctyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-phenylheptyl]thiophene-2-sulfonamide;

5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-phenylpropyl]thiophene-2-sulfonamide;
S-chloro-N-[(1S,2S)-1-(hydroxymethyl)-4-methyl-2-phenylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)propyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide;
S-chloro-N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)-4-methylpentyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)octyl]thiophene-2-sulfonamide;
5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-isopropyloctyl]thiophene-2-sulfonamide;
N-[(1S,2S)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)propyl]-5-chlorothiophene-2-sulfonamide;
N-[(1S,2S)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)butyl]-5-chlorothiophene-2-sulfonamide;
N-[(1S,2S)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)-4-methylpentyl]-5-chlorothiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2,4-dimethylpentyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-methyloctyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S)-2-ethyl-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-2-ethyl-1-(hydroxymethyl)-4-methylpentyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-2-ethyl-1-(hydroxymethyl)pentyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-1-(hydroxymethyl)-4-methyl-2-propylpentyl]thiophene-2-sulfonamide;

5-bromo-N-[(1S,2S)-2-ethyl-1-(hydroxymethyl)heptyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-isobutylheptyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-(4-methoxyphenyl)heptyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-pentyloctyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-phenylpropyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-phenylbutyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-1-(hydroxymethyl)-4-methyl-2-phenylpentyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-1-(hydroxymethyl)-4-methyl-2-pyridin-3-ylpentyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)propyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)-4-methylpentyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)octyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-2-ethyl-1-(hydroxymethyl)-3-methylbutyl]thiophene-2-sulfonamide;
5-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-isopropyl-4-methylpeniyl]thiophene-2-sulfonamide;
N-[(1S,2S)-2-[1,1'-biphenyl]-4-yl-1-(hydroxymethyl)butyl]-5-bromothiophene-2-sulfonamide;
5-chloro-N-[(1S,2R)-2-ethyl-1-(hydroxymethyl)octyl]thiophene-2-sulfonamide;

5-chloro-N-[(1S,2S)-2-ethyl-1-(hydroxymethyl)octyl]thiophene-2-sulfonamide;

5-bromo-N-[(1S,2R)-2-ethyl-1-(hydroxymethyl)octyl]thiophene-2-sulfonamide;

5-bromo-N-[(1S,2S)-2-ethyl-1-(hydroxymethyl)octyl]thiophene-2-sulfonamide;

5-chloro-N-[(1S)-1-(hydroxymethyl)-2-(methylamino)butyl]-2-thiophenesulfonamide;

5-chloro-N-[(1S)-2-(ethylamino)-2-(hydroxymethyl)propyl]-2-thiophenesulfonamide;

5-chloro-N-[(1S)-2-[(2-hydroxyethyl)amino]-1-(hydroxymethyl)propyl]-2-thiophenesulfonamide;

5-chloro-N-[(1S)-2-[(2-hydroxyethyl)amino]-1-(hydroxymethyl)butyl]-2-thiophenesulfonamide;

5-chloro-N-[(1S)-2-[(2-hydroxyethyl)amino]-1-(hydroxymethyl)heptyl]-2-thiophenesulfonamide;

N-[(1S)-2-(benzylamino)-1-(hydroxymethyl)propyl]-5-chloro-2-thiophenesulfonamide;

N-[(1S)-2-(benzylamino)-1-(hydroxymethyl)butyl]-5-chloro-2-thiophenesulfonamide;

5-chloro-N-[(1S)-2-(cyclopentylamino)-1-(hydroxymethyl)propyl]-2-thiophenesulfonamide;

5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]-N-(2-phenoxyethyl)thiophene-2-sulfonamide;

5-chloro-N-(3-chlorobenzyl)-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;

5-chloro-N-[(S)-2-hydroxy-1-phenylethyl]thiophene-2-sulfonamide;

5-chloro-N-[(S)-1-(hydroxymethyl)-3-methylbutyl]thiophene-2-sulfonamide;

5-chloro-N-[1-(hydroxymethyl)pentyl]thiophene-2-sulfonamide;

5-chloro-N-(2-hydroxy-1,1-dimethylethyl)thiophene-2-sulfonamide;

N-[1,1-bis(hydroxymethyl)propyl]-5-chlorothiophene-2-sulfonamide;

5-chloro-N-[1-(hydroxymethyl)cyclopentyl]thiophene-2-sulfonamide;

5-chloro-N-[(S)-2-cyclohexyl-1-(hydroxymethyl)ethyl]thiophene-2-sulfonamide;

N-[(S)-1-benzyl-2-hydroxyethyl]-5-chlorothiophene-2-sulfonamide;

5-chloro-N-[1-(hydroxymethyl)butyl]thiophene-2-sulfonamide;

5-chloro-N-[(S)-1-(hydroxymethyl)-2,2-dimethylpropyl]thiophene-2-sulfonamide;

5-chloro-N-[(R,R)-2-hydroxy-1-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]thiophene-2-sulfonamide;

5-chloro-N-[(S)-1-(hydroxymethyl)propyl]thiophene-2-sulfonamide;

N-[R-2-(benzylthio)-1-(hydroxymethyl)ethyl]-5-chlorothiophene-2-sulfonamide;

N-[(R,S)-2-(benzyloxy)-1-(hydroxymethyl)propyl]-5-chlorothiophene-2-sulfonamide;

5-chloro-N-[(R,R)-2-hydroxy-1-(hydroxymethyl)propyl]thiophene-2-sulfonamide;

5-bromo-N-[(S)-2-hydroxy-1-phenylethyl]thiophene-2-sulfonamide;

5-bromo-N-[(S)-1-(hydroxymethyl)-3-methylbutyl]thiophene-2-sulfonamide;

5-bromo-N-[1-(hydroxymethyl)pentyl]thiophene-2-sulfonamide;

5-bromo-N-(2-hydroxy-1,1-dimethylethyl)thiophene-2-sulfonamide;

N-[1,1-bis(hydroxymethyl)propyl]-5-bromothiophene-2-sulfonamide 5-bromo-N-[1-(hydroxymethyl)cyclopentyl]thiophene-2-sulfonamide 5-bromo-N-[(S)-2-cyclohexyl-1-(hydroxymethyl)ethyl]thiophene-2-sulfonamide;

5-bromo-N-[(S)-1-(hydroxymethyl)-3-(methylthio)propyl]thiophene-2-sulfonamide;

5-bromo-N-[1-(hydroxymethyl)butyl]thiophene-2-sulfonamide;

5-bromo-N-[(S)-1-(hydroxymethyl)-2,2-dimethylpropyl]thiophene-2-sulfonamide;

N-[R-2-(benzylthio)-1-(hydroxymethyl)ethyl]-5-bromothiophene-2-sulfonamide;

5-bromo-N-(R-2-hydroxy-1-{[(3-methylbenzyl)thio]methyl}ethyl)thiophene-2-sulfonamide;

N-{(S)-1-[4-(benzyloxy)benzyl]-2-hydroxyethyl}-5-bromothiophene-2-sulfonamide;

5-bromo-N-[(R,R)-2-hydroxy-1-(hydroxymethyl)propyl]thiophene-2-sulfonamide;

5-chloro-N-[(S,S)-1-formyl-2-methylbutyl]thiophene-2-sulfonamide;

5-chloro-N-[(S,S)-1-(1-hydroxyethyl)-2-methylbutyl]thiophene-2-sulfonamide;

5-chloro-N-{(S,S)-1-[cyclopentyl(hydroxy)methyl]-2-methylbutyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]octyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]heptyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]hexyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-3-methyl-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-3,3-dimethyl-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-4-methyl-1-[(S)-1-methylpropyl]pentyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]but-3-enyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]pent-4-enyl}thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;

5-chloro-N-{(S,S)-1-[(4-fluorophenyl)(hydroxy)methyl]-2-methylbutyl}thiophene-2-sulfonamide;

5-chloro-N-{(S,S)-1-[(4-chlorophenyl)(hydroxy)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
5-chloro-N-{(S)-2-hydroxy-4-methyl-1-[(S)-1-methylpropyl]pent-3-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S)-2-hydroxy-3-methyl-1-[(S)-1-methylpropyl]but-3-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-1-[hydroxy(4-methoxyphenyl)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,E)-2-hydroxy-3-methyl-1-[(S)-1-methylpropyl]pent-3-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S)-4-(1,3-dioxan-2-yl)-2-hydroxy-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;
5-chloro-N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]hex-5-enyl}thiophene-2-sulfonamide;
5-chloro-N-((S,S)-1-{hydroxy[4-(methylthio)phenyl]methyl}-2-methylbutyl)thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-1-[[4-(dimethylamino)phenyl](hydroxy)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
N-{(S,S)-1-[cyclopentyl(hydroxy)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]octyl}thiophene-2-sulfonamide;
N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]heptyl}thiophene-2-sulfonamide;
N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]hexyl}thiophene-2-sulfonamide;
N-{(S,S)-1-[hydroxy(2-methylphenyl)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
N-{(S)-2-hydroxy-3,3-dimethyl-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;
N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]but-3-enyl}thiophene-2-sulfonamide;

N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]pent-4-enyl}thiophene-2-sulfonamide;
N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;
N-{(S,S)-1-[hydroxy(4-methoxyphenyl)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
N-{(S)-4-(1,3-dioxan-2-yl)-2-hydroxy-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;
N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]hex-5-enyl}thiophene-2-sulfonamide;
N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]pent-3-ynyl}thiophene-2-sulfonamide;
N-((S,S)-1-{hydroxy[4-(methylthio)phenyl]methyl}-2-methylbutyl)thiophene-2-sulfonamide;
N-{(S,S)-1-[[4-(dimethylamino)phenyl](hydroxy)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-1-[(S)-cyclohex-2-en-1-yl(hydroxy)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,S,E)-2-hydroxy-1-[(S)-1-methylpropyl]hex-4-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,R,E)-2-hydroxy-1-[(S)-1-methylpropyl]hex-4-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,R,E)-2-hydroxy-1-[(S)-1-methylpropyl]hept-4-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-2-hydroxy-4-methyl-1-[(S)-1-methylpropyl]pent-4-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,R)-2-hydroxy-4-methyl-1-[(S)-1-methylpropyl]pent-4-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,E)-2-hydroxy-1-[(S)-1-methylpropyl]-5-phenylpent-4-enyl}thiophene-2-sulfonamide;
5-chloro-N-[(S,S)-1-(1-hydroxy-1-methylethyl)-2-methylbutyl]thiophene-2-sulfonamide;

5-chloro-N-{(S)-2-hydroxy-1-[(S)-1-methylpropyl]-2-pentylheptyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-1-[hydroxy(diphenyl)methyl]-2-methylbutyl}thiophene-2-sulfonamide;
N-{(S)-2-allyl-2-hydroxy-1-[(S)-1-methylpropyl]pent-4-enyl}-5-chlorothiophene-2-sulfonamide;
5-chloro-N-{(S)-2-ethyl-2-hydroxy-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;
N-{(S,S)-1-[bis(4-chlorophenyl)(hydroxy)methyl]-2-methylbutyl}-5-chlorothiophene-2-sulfonamide;
5-chloro-N-{(S)-2-hydroxy-2-isopropenyl-3-methyl-1-[(S)-1-methylpropyl]but-3-enyl}thiophene-2-sulfonamide;
5-chloro-N-((S,S)-1-{hydroxy[bis(4-methoxyphenyl)]methyl}-2-methylbutyl)thiophene-2-sulfonamide;
5-chloro-N-{(S,E)-2-hydroxy-3-methyl-2-[(E)-1-methylprop-1-enyl]-1-[(S)-1-methylpropyl]pent-3-enyl}thiophene-2-sulfonamide;
N-{(S)-2-but-3-enyl-2-hydroxy-1-[(S)-1-methylpropyl]hex-5-enyl}-5-chlorothiophene-2-sulfonamide;
5-chloro-N-((S,S)-1-{hydroxy[di(1-naphthyl)]methyl}-2-methylbutyl)thiophene-2-sulfonamide;
5-bromo-N-{(S)-2-ethyl-2-hydroxy-1-[(S)-1-methylpropyl]butyl}thiophene-2-sulfonamide;
5-bromo-N-{(S)-2-hydroxy-2-isopropenyl-3-methyl-1-[(S)-1-methylpropyl]but-3-enyl}thiophene-2-sulfonamide;
5-bromo-N-{(S,E)-2-hydroxy-3-methyl-2-[(E)-1-methylprop-1-enyl]-1- [(S)-1-methylpropyl]pent-3-enyl}thiophene-2-sulfonamide;
5-bromo-N-{(S)-2-but-3-enyl-2-hydroxy-1-[(S)-1-methylpropyl]hex-5-enyl}thiophene-2-sulfonamide;
5-chloro-N-[1-(hydroxymethyl)cyclohexyl]thiophene-2-sulfonamide;
5-chloro-N-[2-(hydroxymethyl)bicyclo[2.2.1]hept-2-yl]thiophene-2-sulfonamide;

5-chloro-N-[1-(hydroxymethyl)-2,3-dihydro-H-inden-1-yl]thiophene-2-sulfonamide;
5-chloro-N-[2-(hydroxymethyl)-2,3-dihydro-H-inden-2-yl]thiophene-2-sulfonamide;
5-bromo-N-[1-(hydroxymethyl)cyclohexyl]thiophene-2-sulfonamide;
5-bromo-N-[2-(hydroxymethyl)bicyclo[2.2.1]hept-2-yl]thiophene-2-sulfonamide;
5-bromo-N-[2-(hydroxymethyl)-2,3-dihydro-H-inden-2-yl]thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-1-[(S)-1-hydroxyethyl]-2-methylbutyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-1-[R-1-hydroxyethyl]-2-methylbutyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-2-hydroxy-1-[(S)-1-methylpropyl]pentyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,R)-2-hydroxy-1-[(S)-1-methylpropyl]pentyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-2-hydroxy-1-[(S)-1-methylpropyl]pent-4-enyl}thiophene-2-sulfonamide;
5-chloro-N-{(S,R)-2-hydroxy-1-[(S)-1-methylpropyl]pent-4-enyl}thiophene-2-sulfonamide;
5-bromo-N-{(S,S)-1-[(S)-1-hydroxyethyl]-2-methylbutyl}thiophene-2-sulfonamide;
5-bromo-N-{(S,S)-1-[R-1-hydroxyethyl]-2-methylbutyl}thiophene-2-sulfonamide;
5-bromo-N-{(S,S)-2-hydroxy-1-[(S)-1-methylpropyl]pentyl}thiophene-2-sulfonamide;
5-bromo-N-{(S,R)-2-hydroxy-1-[(S)-1-methylpropyl]pentyl}thiophene-2-sulfonamide;
5-bromo-N-{(S,S)-2-hydroxy-1-[(S)-1-methylpropyl]pent-4-enyl}thiophene-2-sulfonamide;

5-bromo-N-{(S,R)-2-hydroxy-1-[(S)-1-methylpropyl]pent-4-enyl}thiophene-2-sulfonamide;
S-chloro-N-[(S,S)-2-methyl-1-(2,2,2-trifluoro-1-hydroxyethyl)butyl]thiophene-2-sulfonamide;
5-chloro-N-[1-(1-hydroxybut-3-enyl)cyclohexyl]thiophene-2-sulfonamide;
5-chloro-N-[ 1-( 1-hydroxy-3-methylbut-3-enyl)cyclohexyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-methoxycyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-propoxycyclohexyl)ethyl]thiophene-2-sulfonamide;
N-{(S)-1-[4-(allyloxy)cyclohexyl]-2-hydroxyethyl}-5-chlorothiophene-2-sulfonamide;
N-{(S)-1-[4-(benzyloxy)cyclohexyl]-2-hydroxyethyl}-5-chlorothiophene-2-sulfonamide;
N-[1-acetyl-4-(hydroxymethyl)piperidin-4-yl]-5-chlorothiophene-2-sulfonamide;
N-[(1S)-2-butyl-1-(hydroxymethyl)hexyl]-5-chloro-2-thiophenesulfonamide;
N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]-5-iodo-2-thiophenesulfonamide;
5-fluoro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]-2-thiophenesulfonamide;
N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-benzylaminocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-methylaminocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-ethylaminocyclohexyl)ethyl]thiophene-2-sulfonamide;

5-chloro-N-[(S)-2-hydroxy-1-(4-npropylaminocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-allylaminocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-(3-pyridyl)methylaminocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-morpholinocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-(4-pyridyl)methylaminocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-(2-pyridyl)methylaminocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-(4-(carboethoxymethyl)aminocyclohexyl)ethyl]thiophene-2-sulfonamide;
5-Chloro-N-[(S)-2-hydroxy-1-(4-hydroxycyclohexyl)ethyl]thiophene-2-sulfonamide 5-chloro-N-[(S)-2-ethyl-1-formylbutyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-ethyl-1-(1-hydroxyethyl)butyl]thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-ethyl-1-(1-hydroxy-1-methylethyl)butyl]thiophene-2-sulfonamide;
5-chloro-N-(2-hydroxy-1-tetrahydro-H-thiopyran-4-ylethyl)thiophene-2-sulfonamide;
5-chloro-N-[(S)-2-hydroxy-1-piperidin-4-ylethyl]thiophene-2-sulfonamide;
N-[(S)-2-ethyl-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide;
N-[(S)-2-ethyl-1-(hydroxymethyl)butyl]-5-fluorothiophene-2-sulfonamide;
5-chloro-N-[(S)-1-(2,3-dihydro-H-inden-2-yl)-2-hydroxyethyl]thiophene-2-sulfonamide;
5-chloro-N-{(S,S)-1-[(Z-(hydroxyimino)methyl]-2-methylbutyl}thiophene-2-sulfonamide; and 5-chloro-N-{(S,S)-1-[(E)-(hydroxyimino)methyl]-2-methylbutyl}thiophene-2-sulfonamide.
18. The compound according to claim 1, wherein the compound is 5-chloro-N-[(1S)-2-ethyl-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide.
19. The compound according to claim 1 or 5, wherein X is O, and W, Y
and Z are independently selected from C and CR10.
20. The compound according to claim 19, wherein R6 is halogen, R4 is lower alkyl of S-stereochemistry, R3 is hydrogen, R5 is hydrogen, and R1 and R2 are each hydrogen.
21. The compound according to claim 1, wherein the compound is selected from the group consisting of N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]-2-furansulfonamide and 5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]-2-furansulfonamide.
22. The compound according to claim 1, wherein the compound is 4-[1-(5-chloro-thiophene-2-sulfonylamino)-2-hydroxy-ethyl]-piperidine-1-carboxylic acid tert-butyl ester.
23. The compound according to any of claims 1 to 22, wherein the pharmaceutically acceptable salt is selected from the group consisting of salts of acetic acid, lactic acid, citric acid, tartaric acid, succinic acid, fumaric acid, maleic acid, malonic acid, mandelic acid, malic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, toluenesulfonic acid, salts of bases, and mixtures thereof.
24. A pharmaceutical composition comprising a compound according to any of claims 1 to 23 and a physiologically compatible carrier.
25. A method of inhibiting beta amyloid production in a subject, said method comprising the step of delivering a compound according to any of claims to 23.
26. The method according to claim 25, wherein said compound is delivered orally or by injection.
27. A method of treating a disease selected from the group consisting of Alzheimer's Disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, and Down's syndrome, in a subject, said method comprising the step of administering a compound according to any of claims 1 to 23 to said subject in an amount sufficient to alleviate the symptoms or progress of said disease.
28. Use of the compound according to any of claims 1 to 23, or said acceptable salt thereof, in preparing a medicament.
29. Use of the compound according to any of claims 1 to 23, or said acceptable salt, in preparing a medicament useful for administration to a mammalian subject for inhibiting beta amyloid production.
30. The use according to claim 29, wherein said compound is administered orally or by injection.
31. Use of the compound according to any of claims 1 to 23, or said acceptable salt, in preparing a medicament useful for administration to a mammalian subject for treating a disease selected from the group consisting of Alzheimer's Disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, and Down's syndrome, wherein said compound is administered in an amount sufficient to alleviate the symptoms or progress of said disease.
CA2436526A 2000-12-13 2001-12-11 Heterocyclic sulfonamide inhibitors of beta amyloid production Expired - Fee Related CA2436526C (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003528076A (en) * 2000-03-20 2003-09-24 メルク シャープ エンド ドーム リミテッド Sulfonamide-substituted bridged bicycloalkyl derivatives
NZ526213A (en) * 2000-12-13 2005-05-27 Wyeth Corp Heterocyclic sulfonamide inhibitors of beta amyloid production
US6657070B2 (en) 2000-12-13 2003-12-02 Wyeth Production of chirally pure α-amino acids and N-sulfonyl α-amino acids
BR0214863A (en) * 2001-12-11 2004-12-14 Wyeth Corp Process for the synthesis of chirally pure beta-amino alcohols
RU2321394C2 (en) * 2002-06-11 2008-04-10 Уайт Substituted phenylsulfonamide inhibitors of beta-amyloid secretion
DE60329316D1 (en) * 2002-11-12 2009-10-29 Merck & Co Inc PHENYL ACARBOXAMIDE AS A BETA SEKRETASE INHIBITOR FOR THE TREATMENT OF ALZHEIMER
WO2004092155A1 (en) * 2003-03-31 2004-10-28 Wyeth Fluoro-and trifluoroalkyl-containing heterocyclic sulfonamide inhibitors of beta amyloid production and derivatives thereof
KR20060066057A (en) * 2003-06-30 2006-06-15 다이이찌 세이야꾸 가부시기가이샤 Heterocyclic methyl sulfone derivative
CA2552558A1 (en) * 2004-01-16 2005-08-11 Wyeth Heterocyclic sulfonamide inhibitors of beta amyloid production containing an azole
WO2006078753A1 (en) 2005-01-18 2006-07-27 Elan Pharmaceuticals, Inc. N-substituted heterocyclic sulfonamides
CN101142194B (en) * 2005-03-14 2012-10-10 顶点制药有限责任公司 Benzazole derivatives, compositions, and methods of use as b-secretase inhibitors
TW200800959A (en) * 2005-06-10 2008-01-01 Wyeth Corp Piperazine-piperidine antagonists and agonists of the 5-HT1a receptor
GB0602951D0 (en) * 2006-02-14 2006-03-29 Novartis Ag Organic Compounds
CN101384579A (en) * 2006-02-17 2009-03-11 惠氏公司 Selective n-sulfonylation of 2-amino trifluoroalkyl substituted alcohols
RU2008129797A (en) * 2006-02-17 2010-03-27 Вайет (Us) METHODS FOR PRODUCING SULFONAMIDE-SUBSTITUTED ALCOHOLS AND THEIR INTERMEDIATE COMPOUNDS
CA2649396A1 (en) * 2006-04-21 2007-11-08 Wyeth Production of chirally pure amino alcohol intermediates, derivatives thereof, and uses thereof
US7550629B2 (en) * 2006-04-21 2009-06-23 Wyeth Trifluoromethyl-containing phenylsulfonamide beta amyloid inhibitors
US7476762B2 (en) * 2006-04-21 2009-01-13 Wyeth Methods for preparing sulfonamide compounds
TW200808740A (en) * 2006-06-09 2008-02-16 Wyeth Corp Succinate salts of 6-methoxy-8-[4-(1-(5-fluoro)-quinolin-8-yl-piperidin-4-yl)-piperazin-1-yl]-quinoline and crystalline forms thereof
TW200808741A (en) * 2006-06-09 2008-02-16 Wyeth Corp 6-methoxy-8-[4-(1-(5-fluoro)-quinolin-8-yl-piperidin-4-yl)-piperazin-1-yl]-quinoline hydrochloric acid salts
TW200811144A (en) * 2006-06-09 2008-03-01 Wyeth Corp Crystalline forms of 6-methoxy-8-[4-(1-(5-fluoro)-quinolin-8-yl-piperidin-4-yl)-piperazin-1-yl]-quinoline
WO2008059238A1 (en) * 2006-11-17 2008-05-22 Astrazeneca Ab Benzenesulfonamide compounds as edg-1 antagonists useful in the treatment of cancer
WO2008064320A2 (en) * 2006-11-21 2008-05-29 University Of Virginia Patent Foundation Hydrindane analogs having sphingosine 1-phosphate receptor agonist activity
US20080262228A1 (en) * 2006-11-28 2008-10-23 Wyeth Metabolites of 5-fluoro-8- quinoline and methods of preparation and uses thereof
CL2008000119A1 (en) * 2007-01-16 2008-05-16 Wyeth Corp COMPOUNDS DERIVED FROM PIRAZOL, ANTAGONISTS OF THE NICOTINIC ACETILCOLINE RECEIVER; PHARMACEUTICAL COMPOSITION; AND USE IN THE TREATMENT OF DISEASES SUCH AS SENILE DEMENTIA, ALZHEIMER AND SCHIZOPHRENIA.
EP2121633A2 (en) 2007-02-12 2009-11-25 Merck & Co., Inc. Piperazine derivatives for treatment of ad and related conditions
AR067534A1 (en) * 2007-07-16 2009-10-14 Wyeth Corp PROCESS FOR THE PREPARATION OF TRIFLUOROALQUIL - PHENYL SULFONAMIDS AND HETEROCICLIC SULFONAMIDS
CL2008002059A1 (en) * 2007-07-16 2008-11-14 Wyeth Corp Method of preparation of heterocyclic sulfonamides; intermediate compounds used in the described method; and the methods of preparing said intermediaries.
EP2193117A1 (en) * 2007-07-16 2010-06-09 Wyeth a Corporation of the State of Delaware Inhibitors of beta amyloid production
WO2009082437A2 (en) 2007-12-21 2009-07-02 Ligand Pharmaceuticals Incorporated Selective androgen receptor modulators (sarms) and uses thereof
AR070120A1 (en) * 2008-01-11 2010-03-17 Wyeth Corp DERIVATIVES OF ARIL SULFONAMIDE CONTAINING O-SULFATE AND O-PHOSPHATE, USEFUL AS BETA-AMYLOID INHIBITORS, PREPARATION PROCESS OF THE SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
WO2009128057A2 (en) 2008-04-18 2009-10-22 UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN et al Psycho-pharmaceuticals
EP3586839A1 (en) 2008-07-28 2020-01-01 Blanchette Rockefeller Neurosciences, Institute Pkc-activating compounds for the treatment of neurodegenerative diseases
JP2013514287A (en) 2009-12-17 2013-04-25 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング Inhibitors of sphingosine kinase
US9802954B2 (en) 2011-08-24 2017-10-31 Boehringer Ingelheim International Gmbh Piperidino-dihydrothienopyrimidine sulfoxides and their use for treating COPD and asthma
CN105142627B (en) 2013-01-18 2019-06-21 卡尔迪奥克斯尔制药公司 Medical composition comprising nitroxyl donors
CN104370769B (en) * 2013-08-14 2017-05-31 重庆博腾制药科技股份有限公司 A kind of method for preparing hydroxyadamantane glycine derivative
WO2015108988A2 (en) 2014-01-17 2015-07-23 Ligand Pharmaceuticals, Inc. Methods and compositions for modulating hormone levels
US11046668B2 (en) 2016-03-11 2021-06-29 Ohio State Innovation Foundation Small molecule antimicrobials
DE202022106287U1 (en) 2022-11-09 2022-11-21 Ahmad Salawi A method for the synthesis and biological evaluation of new sulfonamide analogues

Family Cites Families (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US656536A (en) * 1899-12-28 1900-08-21 David Fitzgibbons Boiler.
US3376523A (en) * 1966-12-27 1968-04-02 Univ California Transient-suppressing magnetic transmission line
US5464853A (en) 1993-05-20 1995-11-07 Immunopharmaceutics, Inc. N-(5-isoxazolyl)biphenylsulfonamides, N-(3-isoxazolyl)biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
US5591761A (en) 1993-05-20 1997-01-07 Texas Biotechnology Corporation Thiophenyl-, furyl-and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
US5514691A (en) 1993-05-20 1996-05-07 Immunopharmaceutics, Inc. N-(4-halo-isoxazolyl)-sulfonamides and derivatives thereof that modulate the activity of endothelin
US5571821A (en) 1993-05-20 1996-11-05 Texas Biotechnology Corporation Sulfonamides and derivatives thereof that modulate the activity of endothelin
US5594021A (en) 1993-05-20 1997-01-14 Texas Biotechnology Corporation Thienyl-, furyl- and pyrrolyl sulfonamides and derivatives thereof that modulate the activity of endothelin
KR920019763A (en) 1991-04-26 1992-11-19 모리다 가즈라 Azole compounds, preparation methods and uses thereof
GB9110722D0 (en) 1991-05-17 1991-07-10 Fujisawa Pharmaceutical Co Amine derivatives
US5766846A (en) 1992-07-10 1998-06-16 Athena Neurosciences Methods of screening for compounds which inhibit soluble β-amyloid peptide production
US5968942A (en) * 1992-08-25 1999-10-19 G. D. Searle & Co. α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
JP3599287B2 (en) * 1993-04-28 2004-12-08 三菱化学株式会社 Sulfonamide derivative
US6342610B2 (en) * 1993-05-20 2002-01-29 Texas Biotechnology Corp. N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
US6376523B1 (en) 1994-05-20 2002-04-23 Texas Biotechnology Corporation Benzenesulfonamides and the use thereof to modulate the activity of endothelin
NZ264143A (en) 1993-08-09 1996-11-26 Lilly Co Eli Use of an aspartyl protease inhibitor to inhibit beta-amyloid peptide production
US5519040A (en) 1994-04-29 1996-05-21 Allergan Substituted thiazole sulfonamides as antiglaucoma agents
US5561146A (en) * 1994-06-10 1996-10-01 Bristol-Myers Squibb Company Modified guanidino and amidino thrombin inhibitors
US5624937A (en) 1995-03-02 1997-04-29 Eli Lilly And Company Chemical compounds as inhibitors of amyloid beta protein production
JPH09136878A (en) * 1995-09-12 1997-05-27 Ono Pharmaceut Co Ltd Tetrazole derivative
EP0761680A3 (en) * 1995-09-12 1999-05-06 Ono Pharmaceutical Co., Ltd. Tetrazole compounds having Interleukin-1beta converting enzyme inhibitory activity
CA2238175A1 (en) * 1995-11-28 1997-06-19 Cephalon, Inc. D-amino acid derived inhibitors of cysteine and serine proteases
WO1997024340A1 (en) 1995-12-27 1997-07-10 Takeda Chemical Industries, Ltd. Oxazole derivatives, their production and use
JPH09235276A (en) * 1995-12-27 1997-09-09 Takeda Chem Ind Ltd Oxazole derivative, production of the same and use of the same
US5877193A (en) * 1996-07-19 1999-03-02 Hoffmann-La Roche Inc. Use of N-(4-aryl-thiazol-2-yl)-sulfonamides
JP2000515153A (en) 1996-07-22 2000-11-14 モンサント カンパニー Thiolsulfonamide metalloprotease inhibitor
US5703129A (en) 1996-09-30 1997-12-30 Bristol-Myers Squibb Company 5-amino-6-cyclohexyl-4-hydroxy-hexanamide derivatives as inhibitors of β-amyloid protein production
JP2001502330A (en) * 1996-10-11 2001-02-20 ワーナー―ランバート・コンパニー Sulfonamide-substituted aspartate interleukin-1β converting enzyme inhibitor
US5985930A (en) 1996-11-21 1999-11-16 Pasinetti; Giulio M. Treatment of neurodegenerative conditions with nimesulide
HUP0001383A3 (en) 1996-11-22 2001-11-28 Lilly Co Eli N-(aryl/heteroaryl) amino acid derivatives, pharmaceutical compositions comprising same and their use
DE19650196A1 (en) * 1996-12-04 1998-06-10 Bayer Ag Thienylsulfonylamino (thio) carbonyl compounds
GB9725138D0 (en) * 1997-11-27 1998-01-28 Pharmacia & Upjohn Spa Thiophenesulfonamide compounds
JPH11343279A (en) 1998-03-16 1999-12-14 Shionogi & Co Ltd Sulfonamide derivative and tnf-alfa production inhibitor containing the same
US5981168A (en) 1998-05-15 1999-11-09 The University Of British Columbia Method and composition for modulating amyloidosis
EA200001247A1 (en) * 1998-06-03 2001-08-27 Джи Пи Ай Нил Холдингс, Инк. N-BONDED SULPHONAMIDES OF N-HETEROCYCLIC CARBONIC ACIDS OR ISATERES OF CARBONIC ACIDS
US7410995B1 (en) 1998-08-14 2008-08-12 Gpi Nil Holdings Inc. N-linked sulfonamide of heterocyclic thioesters for vision and memory disorders
AU773273B2 (en) 1999-02-26 2004-05-20 Bristol-Myers Squibb Company Novel sulfonamide compounds and uses thereof
CN1347411A (en) 1999-04-19 2002-05-01 盐野义制药株式会社 Sulfonamide derivs. having oxadiazole rings
EP1088815A1 (en) * 1999-09-28 2001-04-04 Applied Research Systems ARS Holding N.V. Pharmaceutically active sulfonyl amino acid derivatives
EP1088821A1 (en) * 1999-09-28 2001-04-04 Applied Research Systems ARS Holding N.V. Pharmaceutically active sulfonamide derivatives
EP1222176A1 (en) * 1999-10-08 2002-07-17 Bristol-Myers Squibb Pharma Company AMINO LACTAM SULFONAMIDES AS INHIBITORS OF A$g(b) PROTEIN PRODUCTION
US6657070B2 (en) * 2000-12-13 2003-12-02 Wyeth Production of chirally pure α-amino acids and N-sulfonyl α-amino acids
NZ526213A (en) * 2000-12-13 2005-05-27 Wyeth Corp Heterocyclic sulfonamide inhibitors of beta amyloid production
JP4615861B2 (en) 2001-12-11 2011-01-19 ワイス・エルエルシー Production of chirally pure α-amino acids and N-sulfonyl α-amino acids
BR0214863A (en) 2001-12-11 2004-12-14 Wyeth Corp Process for the synthesis of chirally pure beta-amino alcohols
RU2321394C2 (en) * 2002-06-11 2008-04-10 Уайт Substituted phenylsulfonamide inhibitors of beta-amyloid secretion
WO2004092155A1 (en) 2003-03-31 2004-10-28 Wyeth Fluoro-and trifluoroalkyl-containing heterocyclic sulfonamide inhibitors of beta amyloid production and derivatives thereof

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