Author: claimsbot

We claim:

1. An indole compound represented by the formula (I), or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof;
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wherein
R1 is selected from groups (a), (b), and (c) wherein;
(a) is C7-C20 alkyl, C7-C20 haloalkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents; or
(c) is the group -(L1)-R11; where, -(L1)- is a divalent linking group of 1 to 8 atoms and where R11 is a group selected from (a)
or (b);

R2 is hydrogen, or a group containing 1 to 4 non-hydrogen atoms plus any required hydrogen atoms;
R3 is -(L3)- Z, where -(L3)- is a divalent linker group selected from a bond or a divalent group selected from:
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and Z is selected from a group represented by the formulae,
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wherein, X is oxygen or sulfur; and Ra is selected from hydrogen, C1-C8 alkyl, aryl, C1-C8 alkaryl, C1-C8 alkoxy, aralkyl and CN;
R4 is the group, -(Lh)-(hydroxyfunctional amide); wherein -(Lh)-, is an hydroxyfunctional amide linker having an hydroxyfunctional amide linker length of 1 to 8;
R5 is selected from hydrogen, a non-interfering substituent, or the group, -(La)-(acidic group); wherein -(La)-, is an acid linker having an acid linker length of 1 to 8;
R6 and R7 are selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituent(s), heterocyclic radicals, and heterocyclic radical substituted with non-interfering substituent(s).
2. The compound of claim 1 wherein R2 is hydrogen, C1-C4 alkyl, C2-C4 alkenyl, O(C1-C3 alkyl), S(C1-C3 alkyl), C3-C4 cycloalkyl, CF3, halo, NO2, CN, or SO3.
3. The compound of claim 1 wherein the hydroxyfunctional amide linker group, -(Lh)-, for R4 is selected from a group represented by the formula;
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where Q2 is selected from the group (CH2), O, NH, C(O), and S, and each R40 is independently selected from hydrogen, C1-C8 alkyl, aryl, C1-C8 alkaryl, C1-C8 alkoxy, aralkyl, and halo.
4. The compound of claim 1 wherein the hydroxyfunctional amide linker group, -(Lh)-, for R4 is a divalent group selected from,
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where R40, R41, R42, and R43 are each independently selected from hydrogen, C1-C8 alkyl.
5. The compound of claim 1 wherein the acid linker, -(La)-, for R5 is selected from a group represented by the formulae consisting of;
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wherein R54, R55, R56 and R57 are each independently hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, or halo.
6. The compound of claim 1 wherein R5 is the group, -(La)-(acidic group) and wherein the (acidic group) is selected from the group:
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where R80 is a metal or C1-C8 alkyl and R81 is an organic substituent or CF3.
7. The compound of claim 1 wherein for R3, Z is the group represented by the formula;
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and the linking group -(L3)- is a bond; and Ra is hydrogen, methyl, ethyl, propyl, isopropyl, phenyl or benzyl.
8. The compound of claim 1 wherein for R3, Z is the group represented by the formula;
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and the linking group -(L3)- is a bond; and Ra is hydrogen.
9. The compound of claim 1 wherein for R3, Z is the group represented by the formula;
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and the linking group -(L3)- is a bond.
10. The compound of claim 1 wherein for R3, Z is the group represented by the formula;
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and the linking group -(L3)- is a bond.
11. The compound of claim 1 wherein, for R6 the non-interfering substituent is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolulyl, xylenyl, biphenyl, C1-C8 alkoxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C1-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C8 alkylsulfinyl, C1-C8 alkylsulfonyl, C2-C8 haloalkoxy, C1-C8 haloalkylsulfonyl, C2-C8 haloalkyl, C1-C8 hydroxyalkyl, C(O)O(C1-C8 alkyl), (CH2)nO(C1-C8 alkyl), benzyloxy, phenoxy, phenylthio, (CONHSO2R), CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, (CH2)nCO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, SO3H, thioacetal, thiocarbonyl, or carbonyl; where n is from 1 to 8.
12. The compound of claim 1 wherein for R1 the divalent linking group -(L1)- is selected from a group represented by the formulae (Ia), (Ib), (Ic), (Id), (Ie), and (If):
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where Q1 is a bond or any of the divalent groups Ia, Ib, Ic, Id, and Ie and R10 is independently H, C1-8 alkyl, C1-8 haloalkyl or C1-8 alkoxy.
13. The compound of claim 1 wherein the linking group -(L1)- of R1 is (CH2) or (CH2CH2).
14. The compound of claim 1 wherein the linking group -(L11)- of R11 is a bond and R11 is (CH2)mR12 wherein m is an integer from 1 to 6, and R12 is a group represented by the formula:
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wherein a, c, e, n, q, and t are independently an integer from 0 to 2, R13 and R14 are independently selected from a halogen, C1 to C8 alkyl, C1 to C8 alkyloxy, C1 to C8 alkylthio, aryl, heteroaryl, and C1 to C8 haloalkyl, is an oxygen atom or a sulfur atom, L5 is a bond, (CH2)v-, CC, CC, O, or S, v is an integer from 0 to 2, is CH2 or (CH2)2, is an oxygen atom or a sulfur atom, b is an integer from 0 to 3, d is an integer from 0 to 4, f, p, and w are independently an integer from 0 to 5, r is an integer from 0 to 7, and u is an integer from 0 to 4, or is (e) a member of (d) substituted with at least one substituent selected from the group consisting of C1 to C6 alkyl, C1 to C8 alkyloxy, C1 to C8 haloalkyloxy, C1 to C8 haloalkyl, aryl, and a halogen.
15. The compound of claim 1 wherein for R1 the group R11 is a substituted or unsubstituted carbocyclic radical selected from the group consisting of cycloalkyl, cycloalkenyl, phenyl, spiro5.5undecanyl, naphthyl, norbornanyl, bicycloheptadienyl, tolulyl, xylenyl, indenyl, stilbenyl, terphenylyl, diphenylethylenyl, phenyl-cyclohexenyl, acenaphthylenyl, and anthracenyl, biphenyl, bibenzylyl and related bibenzylyl homologues represented by the formula (a):
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where n is a number from 1 to 8.
16. The compound of claim 12 wherein for R1 the combined group -(L1)-R11 is selected from the groups;
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where R12 is a radical independently selected from halo, C1-C10alkyl, C1-C10 alkoxy, S (C1-C10 alkyl), and C1-C10 haloalkyl, C1-C10 hydroxyalkyl and t is a number from 0 to 5 and u is a number from 0 to 4.
17. The compound of claim 1 wherein for R1 the radical R11 is a substituted or unsubstituted heterocyclic radical selected from pyrrolyl, pyrrolodinyl, piperidinyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, phenylimidazolyl, triazolyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, indolyl, carbazolyl, norharmanyl, azaindolyl, benzofuranyl, dibenzofuranyl, dibenzothiophenyl, indazolyl, imidazo(1.2-A)pyridinyl, benzotriazolyl, anthranilyl, 1,2-benzisoxazolyl, benzoxazolyl, benzothiazolyl, purinyl, pyridinyl, dipyridylyl, phenylpyridinyl, benzylpyridinyl, pyrimidinyl, phenylpyrimidinyl, pyrazinyl, 1,3,5-triazinyl, quinolinyl, phthalazinyl, quinazolinyl-morpholino, thiomorpholino, homopiperazinyl, tetrahydrofuranyl, tetrahydropyranyl, oxacanyl, 1,3-dioxolanyl, 1,3-dioxanyl, 1,4-dioxanyl, tetrahydrothiopheneyl, pentamethylenesulfadyl, 1,3-dithianyl, 1,4-dithianyl, 1,4-thioxanyl, azetidinyl, hexamethyleneiminium, heptamethyleneiminium, piperazinyl or quinoxalinyl.
18. The compound of claim 1 wherein R4 is the group, -(LC)-(hydroxyfunctional amide group) and wherein the (hydroxyfunctional amide group) is:
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and R4a is independently selected from the group consisting of OH, (C1-C6)alkoxy, (C7-C1-4)alkaryloxy, (C2-C8)alkenyloxy, (C7-C14) aralkyloxy, (C7-C14)aralkenyloxy and aryloxy; and wherein R4b is independently selected from the group consisting of H, (C1-C6)alkyl, arylalkyl, heteroaryl and aryl.
19. An indole compound represented by the formula (II), or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof;
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wherein
R22 is selected from hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, F, CF3, Cl, Br, or OCH3;
R4a is independently selected from the group consisting of OH, (C1-C6)alkoxy, (C7-C14)alkaryloxy, (C2-C8)alkenyloxy, (C7-C14) aralkyloxy, (C7-C14)aralkenyloxy and aryloxy; and R4b is H, (C1-C6)alkyl, arylalkyl, heteroaryl or aryl and -(Lh)- is a divalent group selected from;
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where R40, R41, R42, and R43 are each independently selected from hydrogen or C1-C8 alkyl.
R16 is selected from hydrogen, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 alkylthio C1-C8 haloalkyl, C1-C8 hydroxyalkyl, and halo.
R13 is selected from hydrogen and C1-C8 alkyl, C1-C8 alkoxy, S(C1-C8 alkyl), C1-C8 haloalkyl, C1-C8 hydroxyalkyl, phenyl, halophenyl, and halo, and t is an integer from 0 to 5.
20. A compound of claim 1 selected from the group consisting of:
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylm thyl)-1H-indol-4-yloxy-N-(hydroxy)acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(methyloxy) acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-phenylmethyl)-1H-indol-4-yloxy-N-(methyl)-N-(methyloxy)acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(hydroxy)-N-(methyl)acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(ethyloxy) acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(2-propenyloxy) acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(hydroxy)-N-(2-propyl)acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(tert-butyloxy)acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-2-(methyl)propyloxyacetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(phenylmethyloxy) acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-phenylmethyl)-1H-indol-4-yloxy-N-(methyl)-N-(phenylmethyloxy) acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(phenyloxy) acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1H-(phenylmethyl)-1H-indol-4-yloxy-N-(methyl)-N-(phenyloxy) acetamide;
2-3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(cyclohexyl)-N-(hydroxy)acetamide; and
2-3-(2-Amino-2-oxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yloxy-N-(hydroxy)acetamide.
21. An indole compound represented by the formulae (C1), (C2), (C3), (C4), (C5), (C6), (C7), (C8), (C9), (C10), (C11), (C12), (C13), (C14) or (C15);
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or pharmaceutically acceptable salts or prodrugs thereof.
22. A pharmaceutical formulation comprising a indole compound as claimed in claim 1 together with a pharmaceutically acceptable carrier or diluent therefor.
23. A method of inhibiting sPLA2 mediated release of fatty acid comprising: contacting sPLA2 with a therapeutically effective amount of indole compound as claimed in claim 1.
24. A method of treating a mammal, including a human, to alleviate the pathological effects of Inflammatory Diseases; wherein the method comprises administering to said mammal a thrapeutically effective amount of an indole compound as claimed in claim 1.
25. A compound of claim 1 or a pharmaceutical formulation containing an effective amount of the compound of claim 1 useful for the treatment andor amelioration of Inflammatory Diseases.
26. A compound of claim 1 or a pharmaceutical formulation containing an effective amount of the compound of claim 1 for useful for inhibiting sPLA2 mediated release of fatty acid.
27. Use of a pharmaceutical composition comprising sPLA2 inhibitor compounds according to claim 1 and mixtures thereof for the manufacture of a medicament for the treatment of Inflammatory Diseases.

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 fuel cap, comprising a cap main body that is attached to a tank opening of a fuel tank, and a pressure regulating valve that is received in the cap main body and opens and closes an inner-cap flow path formed in the cap main body to regulate an inner pressure of the fuel tank,
the pressure regulating valve including a positive pressure valve that opens when the inner pressure of the fuel tank rises above a preset positive pressure level, and a negative pressure valve that opens when the inner pressure of the fuel tank lowers below a preset negative pressure level,
wherein the positive pressure valve includes a positive pressure valve plug that opens and closes a first valve flow path formed as part of the inner-cap flow path, and a second valve flow path that is formed through the positive pressure valve plug and formed as part of the inner-cap flow path, and
the negative pressure valve includes a negative pressure valve plug that opens and closes the second valve flow path,
wherein the pressure regulating valve further includes a flow path formation member located in an upstream of the first valve flow path, the flow path formation member having a path that leads an outside air into the second valve flow path in an open position of the negative pressure valve.
2. The fuel cap in accordance with claim 1, wherein the positive pressure valve includes a first spring that has one end supported by a support member provided on the cap main body and the other end applying a pressing force to the positive pressure valve plug in a closing direction, and
the positive pressure valve plug has a seating element that is arranged to face the first valve flow path and is seated on a first seat element provided on the cap main body to close the first valve flow path, and a second seat element that is arranged to face the second valve flow path.
3. The fuel cap in accordance with claim 2, wherein the negative pressure valve includes a second spring that applies a pressing force to the negative pressure valve plug in a closing direction.
4. The fuel cap in accordance with claim 1, wherein the positive pressure valve includes a valve support member supporting the positive pressure valve plug, and
the flow path formation member includes a tubular body formed integrally with the valve support member.
5. The fuel cap in accordance with claim 1, wherein the support member includes an inner cover attached to the cap main body, and
the flow path formation member includes a tubular body formed integrally with the inner cover.
6. The fuel cap in accordance with claim 2, wherein the first spring is a coil spring, and
the flow path formation member is arranged to go through an inner space of the first spring.
7. The fuel cap in accordance with claim 1, wherein the flow path formation member includes a tubular body formed integrally with the positive pressure valve plug.

1. An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of:
a nucleic acid sequence that encodes a non-immunogenic fusion protein that comprises a non-IL-15 signal peptide linked to IL-15 protein or a functional fragment thereof and
a nucleic acid sequence that encodes a fusion protein that comprises IL-15 protein or a functional fragment thereof, linked to a non-IL-15 signal peptide that is from a gene that is from the same species as the IL-15.
2. The isolated nucleic acid molecule of claim 1 that encodes an IgE signal peptide.
3. The isolated nucleic acid molecule of claim 1 that encodes a fusion protein consists of a non-IL-15 signal peptide linked to IL-15 protein or a functional fragment thereof.
4. The isolated nucleic acid molecule of claim 1 that encodes IL-15 protein or a functional fragment thereof that is free of IL-15 signal peptide.
5. The isolated nucleic acid molecule of claim 1 wherein the nucleic acid sequence that the IL-15 protein or functional fragment thereof is free of IL-15 Kozak region andor IL-15 5\u2032 untranslated region andor IL-15 3\u2032 untranslated region.
6. The isolated nucleic acid molecule of claim 1 further comprising a nucleotide sequence that encodes CD40L or a functional fragment thereof.
7. (canceled)
8. The isolated nucleic acid molecule of claim 1 further comprising a nucleic acid sequence that encodes an immunogen.
9. The isolated nucleic acid molecule of claim 8 wherein said immunogen is a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases.
10. (canceled)
11. The isolated nucleic acid molecule of claim 9 wherein said pathogen antigen is from a pathogen selected from the group consisting of HIV, HSV, HCV, and WNV.
12.-13. (canceled)
14. The isolated nucleic acid molecule of claim 1 wherein said isolated nucleic acid molecule is a plasmid.
15. The nucleic acid molecule of claim 1 incorporated into a viral vector.
16. A composition comprising a nucleic acid molecule of claim 1.
17. The composition of claim 16 wherein said composition further comprises a nucleic acid molecule that comprises a nucleic acid sequence that encodes an immunogen.
18. The composition of claim 17 wherein said immunogen is a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases.
19. The composition of claim 18 wherein said pathogen antigen is from a pathogen selected from the group consisting of HIV, HSV, HCV, and WNV.
20. The composition of claim 16, wherein the nucleic acid molecule further comprises a nucleotide sequence that encodes CD40L.
21. An injectable pharmaceutical composition comprising the nucleic acid molecule of claim 1.
22. A recombinant vaccine comprising the nucleic acid molecule of claim 1.
23. The recombinant vaccine of claim 22 wherein said recombinant vaccine is a recombinant vaccinia vaccine.
24.-28. (canceled)
29. The composition of claim 16 that further comprises: nucleic acid molecule that comprises a nucleotide sequence that encodes CD40L protein.
30.-53. (canceled)
54. An injectable pharmaceutical composition comprising the composition of claim 16.

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 holding mechanism for foldable side rails, comprising:
an upper horizontal rail member;
a lower horizontal rail member;
at least two stanchion members pivotally rotatably connected between the upper horizontal rail member and the lower horizontal rail member, forming a parallel link mechanism, the holding mechanism keeping the stanchion members erect, and is disposed at an end of the upper horizontal rail member; and
a mechanism support member connected to at least one of the stanchion members provided at said end, and comprising:
a spring;
a stopper pin set capable of advancing and receding;
a stopper pin set disposed to receive the stopper pin on one end and contact the spring on the other;
wherein the at least one of the stanchion members has a fitting hole for allowing the stopper pin set to be fitted in it when the stanchion members are kept erect;
a mechanically driven trigger site;
a release lever engaged with the mechanically driven trigger site provided in connection with the stopper pin set, for making the stopper pin set recede against the force of the spring;
a play mechanism provided between the release lever and the mechanically driven trigger site;
a release prevention mechanism preventing the movement of the release lever in the release allowing direction, the play mechanism configured so that the stopper pin can be automatically fitted into the fitting hole when the upper and lower horizontal rail members are raised; and
a cover enclosing at least one of the spring, stopper pin set, cylinder, and release prevention mechanism, having a pocket formed partially in the place where the release lever is pressed for release action,
wherein the spring is disposed between the cover and the cylinder, and
wherein the stopper pin set is biased in the advancing direction by the spring.
2. The holding mechanism for foldable side rails, according to claim 1, wherein the play mechanism comprises a recess formed in the mechanically driven trigger site and opening in the horizontal direction and a pin installed in the release lever and engaged with the recess.
3. The holding mechanism for foldable side rails, according to claim 1, wherein the release prevention mechanism, further comprises a lock member, comprising:
a contact portion to be kept in contact with an upper face of the release lever; and
a recess designed to avoid contact with the contact portion formed in the upper face of the release lever, in the case where the release lever is moved upward for release action, and
wherein the lock member is movably provided in the upper portion of the mechanism support member.
4. The holding mechanism for foldable side rails, according to claim 3, wherein the recess is formed as the lower horizontal one of two horizontal levels.
5. The holding mechanism for foldable side rails, according to claim 3, wherein the lock member is biased by a second spring in the direction in which the release prevention mechanism acts.
6. The holding mechanism for foldable side rails, according to claim 1, wherein:
a first force applied to the release lever to recede the stopper pin acts in a same direction as the recession of the stopper pin, and
a second force applied to the release prevention mechanism acts approximately perpendicular to the first force.
7. The holding mechanism for foldable side rails, according to claim 1, wherein the pocket prevents erroneous operations of the release lever.