1. A 2,4-disubstituted-5-aminocarbonyl-1,3-thiazole compound represented by the following formula 1:
wherein
R1 and R2 are independently selected from the group consisting of a C1-C10 linear alkyl group, a C3-C10 branched alkyl group, and a C1-C10 linear alkyl group substituted with a C3-C10 cycloalkyl group, or
R1 and R2 together with the nitro en atom to which the are attached form a C3-C10 heterocyclic group containing one or more heteroatoms independently selected from N, S and O;
R3 is a carbonyl group substituted with at least one group selected from the group consisting of a C1-C10 linear alkyl group, a C3-C10 branched alkyl group, a C3-C10 cyclic group, a C1-C10 alkoxy group, a C2-C10 alkenyl group, a C2-C10 alkynyl group, a heteroaryl group, an arylalkyl group, a C5-C10 heteroarylalkyl group, and a phenyl or substituted phenyl group; and
R4 is selected from the group consisting of piperidinyl, morpholino, 4-methoxybenzylamino, piperidin-1-yl-ethylamino, pyrrolidin-1-ylethylamino, 2-morpholinoethylamino, 2-morpholinopropylamino, 4-morpholinopiperidin-1-yl, 4-pyrrolidin-1-ylpiperidin-1-yl, 1,4\u2032-bipiperidin-1\u2032-yl, cyclopropylmethylamino, cyclohexylmethylamino, or
R4 is \u2014NRaRb wherein Ra and Rb are independently selected from the group consisting of a hydrogen, C1-C10 linear alkyl group, a C3-C10 branched alkyl group, a C3-C10 cyclic group, an aryl group, a heteroaryl group, an aryl(C1-C10)alkyl group a heteroaryl(C1-C10)alkyl group, or
R4 is a piperazinyl substituted with a group selected from the group consisting of C1-C10 linear alkyl group, a C3-C10 branched alkyl group, a C3-C10 cyclic group, a phenyl or substituted phenyl group, and a heteroaryl group,
wherein the substituted phenyl group in R3 and R4 represents a phenyl group substituted with 1 to 4 substituents independently selected from the group consisting of a halogen atom, a cyano group, a C1-C10 alkyl group, and a C1-C10 alkoxy group, or
a pharmaceutically acceptable salt thereof.
2. The 2,4-disubstituted-5-aminocarbonyl-1,3-thiazole compound of claim 1, wherein
R1 and R2 are independently selected from the group consisting of a C1-C5 linear alkyl group and a C3-C10 branched alkyl group, or
R1 and R2 together with the nitrogen atom to which they are attached form a C5-C7 heterocyclic group containing one or more heteroatoms independently selected from the group consisting of N, S and O;
R3 is a carbonyl group substituted with at least one group selected from the group consisting of a C1-C5 linear alkyl group, a C3-C5 branched alkyl group, a C3-C6 cyclic alkyl group, a C2-C5 alkenyl group, a C2-C5 alkynyl group, a heteroaryl group, an arylalkyl group, a heteroaryl(C5-C10)alkyl group, and a phenyl or a substituted phenyl group; and
R4 is selected from the group consisting of piperidinyl, morpholino, 4-methoxybenzylamino, piperidin-1-yl-ethylamino, pyrrolidin-1-ylethylamino, 2-morpholinoethylamino, 2-morpholinopropylamino, 4-morpholinopiperidin-1-yl, 4-pyrrolidin-1-ylpiperidin-1-yl, 1,4\u2032-bipiperidin-1\u2032-yl, cyclopropylmethylamino, cyclohexylmethylamino, or
R4 is NRaRb wherein Ra and Rb are independently selected from the group consisting of a hydrogen, C2-C7 linear alkyl group, a C3-C7 branched alkyl group, a C3-C7 cyclic group, an aryl group, a heteroaryl group, an aryl(C1-C5)alkyl group a heteroaryl(C1-C5)alkyl group, or
R4 is a piperazinyl substituted with a group selected from the group consisting of C1-C7 linear alkyl group, a C3-C7 branched alkyl group, a C3-C7 cyclic group, a phenyl or substituted phenyl group, and a heteroaryl group,
wherein the substituted phenyl group in R3 and R4 represents a phenyl group substituted with 1 to 4 substituents independently selected from the group consisting of a halogen atom, a C1-C5 alkyl group, and a C1-C5 alkoxy group.
3. A method for treating atopic dermatitis induced by excessive cellular division and proliferation caused by sphingosylphosphorylcholine (SPC), which contains a compound of claim 1, wherein the compound has an antagonistic effect on selective cell proliferation induced by SPC.
4. The method of claim 3, wherein the compound is selected from the group consisting of N-{5-(morpholine-4-carbonyl)-2-2-(piperidin-1-yl)ethylaminothiazol-4-yl}pivalamide, N-2-(benzylamino)-5-(piperidine-1-carbonyl)thiazol-4-ylpivalamide, and N-{2-4-(2-methoxyphenyl)-piperazin-1-yl-5-(piperidine-1-carbonyl)thiazol-4-yl}pivalamide.
5. A skin external agent for inhibiting post-traumatic scar formation and promoting wound healing, the agent containing a compound of claim 1.
6. A method for inhibiting chemotactic cell migration caused by SPC in a cell comprising administering to the cell an effective amount of a compound of claim 1 to inhibit the chemotactic migration or a pharmaceutically acceptable salt thereof as an active ingredient.
7. The method of claim 6, wherein the compound is N-{2-4-(2-methoxyphenyl)-piperazin-1-yl-5-(piperidin-1-carbonyl)thiazol-4-yl}pivalamide.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A mechanical seal comprising a rotating ring and a single-piece mating ring adapted to seal to one another, wherein:
(a) said single-piece mating ring comprises an inner surface, and an outer surface having an outer circumferential flow-channel; wherein said outer circumferential flow-channel comprises a plurality of symmetrically-spaced through-channels that extend from said outer circumferential flow-channel to said inner surface to uniformly disperse a coolant through said mating ring in a direction perpendicular to the outer circumferential flow-channel; wherein said through-channels are sized and shaped to inhibit clogging from any debris in the coolant;
(b) if a coolant is supplied to said outer circumferential flow-channel, said outer circumferential flow-channel allows the coolant to enter said through-channels and to remove heat uniformly from said mechanical seal;
whereby heat transfer at the interface of said rotating ring and said mating ring is substantially greater than would be the heat transfer between an otherwise identical rotating ring and mating ring lacking said outer circumferential flow-channel and through-channels.
2. A mechanical seal as recited in claim 1, additionally comprising a coolant selected from the group consisting of air, nitrogen, water, ethylene glycol, propane, and lubricating oil.
3. A mechanical seal as recited in claim 1, wherein said mating ring is coated with a layer of Ti-containing amorphous hydrocarbon.
4. A mechanical seal as recited in claim 1, wherein said mating ring is fabricated from a material selected from the group consisting of stainless steel, 17-4 PH stainless steel, Ni-resist, stellite, titanium, silicon carbide, silicon nitride, and graphite composites.
5. A mechanical seal as recited in claim 1, wherein each of said through-channels has a surface area greater than about 0.007 in2.
6. A mechanical seal as recited in claim 1, wherein said through-channels have an edge-to-edge spacing greater than about 0.06 in.