1. A prolapse repair system, comprising:
an eyelet portion;
first and second flexible spanning members extending from the eyelet portion, at least one of the first and second flexible spanning members including a loop portion distal the eyelet portion, wherein the loop portion is operatively engageable with vaginal vault tissue; and
an extension arm having at least a mesh portion and a tissue anchor, the extension arm adjustably engageable with the eyelet portion, and the tissue anchor engageable with tissue a distance away from the vaginal vault tissue.
2. The system of claim 1, wherein the eyelet portion is a locking eyelet having a plurality of inward radiating teeth.
3. The system of claim 1, further including a locking eyelet adjustably engageable with the extension arm.
4. The system of claim 1, wherein the first and second flexible spanning members are suture members.
5. The system of claim 4, wherein the suture members are constructed at least in part of a prolene material.
6. The system of claim 1, wherein the extension arm further includes a polymer rod portion extending from the mesh portion and slidable within the eyelet portion.
7. The system of claim 1, wherein each of the first and second flexible spanning members include a loop portion.
8. The system of claim 7, wherein the loop portions of the first and second flexible extension members are engageable with the vaginal vault tissue via sutures.
9. The system of claim 1, further including an introducer needle to engage the tissue anchor with the tissue a distance away from the vaginal vault tissue.
10. The system of claim 1, further including a locking eyelet and a locking eyelet tool, the locking eyelet adjustably engageable with the extension arm via the locking eyelet tool.
11. The system of claim 1, further including:
a second eyelet portion having first and second flexible spanning members, wherein end portions of the first and second flexible spanning members of the second eyelet portion include a loop operatively engageable with vaginal vault tissue; and
a second extension arm having at least a mesh portion and a tissue anchor, the mesh portion of the second extension arm adjustably engageable with the second eyelet portion, and the tissue anchor of the second extension arm engageable with tissue a distance away from the vaginal vault tissue.
12. A prolapse repair system, comprising:
a first tissue anchor having at least two suture members extending therefrom, each of the at least two suture members of the first tissue anchor having end portions engageable with vaginal vault tissue, wherein the first tissue anchor is engageable with tissue a distance from the vaginal vault tissue; and
a second tissue anchor having at least two suture members extending therefrom, each of the at least two suture members of the second tissue anchor having end portions engageable with vaginal vault tissue, wherein the second tissue anchor is engageable with tissue a distance from the vaginal vault tissue.
13. The system of claim 12, further including a needle to thread the end portion of the at least two suture members of the first tissue anchor to the vaginal vault tissue.
14. The system of claim 13, wherein the needle further threads the end portion of the at least two suture members of the second tissue anchor to the vaginal vault tissue.
15. The system of claim 12, further including a needle to thread the end portion of the at least two suture members of the second tissue anchor to the vaginal vault tissue.
16. The system of claim 12, wherein the at least two suture members of the first and second tissue anchors are constructed at least in part of a prolene material.
17. A prolapse repair system, comprising:
a first eyelet device having first and second suture members extending therefrom, with each of the first and second suture members of the first eyelet device including a loop portion operatively engageable with vaginal vault tissue;
a second eyelet device having first and second suture members extending therefrom, with each of the first and second suture members of the second eyelet device including a loop portion operatively engageable with vaginal vault tissue;
a first extension arm having at least a mesh portion and a tissue anchor, the first extension arm adjustably engageable with the first eyelet device, with the tissue anchor of the first extension arm engageable with tissue a distance away from the vaginal vault tissue; and
a second extension arm having at least a mesh portion and a tissue anchor, the second extension arm adjustably engageable with the second eyelet device, with the tissue anchor of the second extension arm engageable with tissue a distance away from the vaginal vault tissue.
18. The system of claim 17, wherein the first eyelet device and the second eyelet device include a locking eyelet having a plurality of inward extending teeth.
19. The system of claim 17, further including a first locking eyelet adjustably engageable with the mesh of the first extension arm and a second locking eyelet adjustably engageable with the mesh of the second extension arm.
20. The system of claim 17, wherein the tissue anchor of the first extension member is engageable with a first sacrospinous ligament target site and the tissue anchor of the second extension member is engageable with a second sacrospinous ligament target site.
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 compound of formula I
105
wherein
R1 signifies hydrogen or lower alkyl;
R2, R2 signify, independently from each other, hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl;
X signifies O, S or two hydrogen atoms not forming a bridge;
A1A2 signify, independently from each other, phenyl or a 6-membered heterocycle containing 1 or 2 nitrogen atoms;
B is a group of formula
106
wherein
R3 signifies lower alkyl, lower alkenyl, lower alkinyl, benzyl, lower alkyl-cycloalkyl, lower alkyl-cyano, lower alkyl-pyridinyl, lower alkyl-lower alkoxy-phenyl, lower alkyl-phenyl, which is optionally substituted by lower alkoxy, or phenyl, which is optionally substituted by lower alkoxy, or lower alkyl-thienyl, cycloalkyl, lower alkyl-trifluoromethyl or lower alkyl-morpholinyl,
Y signifies O, S or a bond;
Z signifies O or S;
or B is a 5-membered heterocyclic group of formulas
107
wherein
R4 and R5 signifies hydrogen, lower alkyl, lower alkoxy, cyclohexyl, lower alkyl-cyclohexyl or trifluoromethyl, with the proviso that at least one of R4 or R5 has to be hydrogen; as well as their pharmaceutically acceptable salts.
2. A compound of formula IA in accordance with claim 1,
108
wherein B is a group of formula
109
and the remaining substituents are defined in claim 1.
3. A compound of formula IB in accordance with claim 1,
110
wherein
B is a 5-membered heterocyclic group of formulas
111
and the remaining substituents are as defined in claim 1.
4. A compound of formula IA in accordance with claim 2, wherein A1 signifies phenyl, A2 signifies phenyl, X signifies 2 hydrogen atoms not forming a bridge and Z is O.
5. A compound in accordance with claim 4, diphenylacetyl-carbamic acid butyl ester.
6. A compound in accordance with claim 4, diphenylacetyl-carbamic acid ethyl ester.
7. A compound in accordance with claim 4, diphenylacetyl-carbamic acid pent-4-ynyl ester.
8. A compound of formula IA in accordance with claim 2, wherein A1 signifies phenyl, A2 signifies phenyl, X signifies O or S and Z is O.
9. A compound of formula IA in accordance with claim 8, (9H-xanthene-9-carbonyl)-carbamic acid ethyl ester.
10. A compound of formula IA in accordance with claim 8, (9H-xanthene-9-carbonyl)-carbamic acid butyl ester.
11. A compound of formula IA in accordance with claim 8, (9H-thioxanthene-9-carbonyl)-carbamic acid butyl ester.
12. A compound of formula IB in accordance with claim 3, wherein A1 signifies phenyl, A2 signifies phenyl, X signifies 2 hydrogen atoms not forming a bridge and Z is O.
13. A compound of formula IB in accordance with claim 12, N-(5-ethyl-oxazol-2-yl)-2,2-diphenyl-acetamide.
14. A compound of formula IB in accordance with claim 12, N-(5-methyl-oxazol-2-yl)-2,2-diphenyl-acetamide.
15. A compound of formula IB in accordance with claim 12, 2,2-diphenyl-N-(5-propyl-1,3,4oxadiazol-2-yl)-acetamide.
16. A compound of formula IB in accordance with claim 12, N-5-(2-methoxy-ethyl)-1,3,4oxadiazol-2-yl-2,2-diphenyl-acetamide.
17. A compound of formula IB in accordance with claim 12, N-(3-methyl-1,2,4oxadiazol-5-yl)-2,2-diphenyl-acetamide.
18. A compound of formula IB in accordance with claim 12, N-(3-cyclopropyl-1,2,4oxadiazol-5-yl)-2,2-diphenyl-acetamide.
19. A compound of formula IB in accordance with claim 12, N-(5-methyl-1,2,4oxadiazol-3-yl)-2,2-diphenyl-acetamide.
20. A compound of formula IB in accordance with claim 3, wherein A1 signifies phenyl, A2 signifies phenyl, X signifies Oand Z is O.
21. A compound of formula IA in accordance with claim 2, wherein A1 signifies phenyl, A2 signifies phenyl, X signifies O, R2 signifies H and R2 signifies H.
22. A compound of formula IA in accordance with claim 21, wherein Z signifies O, Y signifies Oand R3 signifies lower alkyl.
23. A process for the manufacture of a compound according to claim 1 comprising reacting a compound of the formula
112
with a compound of the formula
113
to a compound of formula
114
wherein the substituents have the significances given in claim 1.
24. A process for the manufacture of a compound according to claim 1 comprising reacting a compound of formula
115
with a compound of the formula
116
to a compound of formula
117
in which G is a suitable leaving group and the other substituents have the significances given in claim 1.
25. A process for the manufacture of a compound according to claim 1 comprising reacting a compound of formula
118
with a compound of the formula
119
to a compound of formula
120
wherein the substituents have the significances given in claim 1.
26. A process for the manufacture of a compound according to claim 1 comprising reacting a compound of formula
121
with a compound of the formula
122
to a compound of formula
123
wherein the substituents have the significances set forth in claim 1. and, if desired, converting a functional group in a compound of formula I into another functional group.
27. A process for the manufacture of a compound according to claim 1 comprising reacting a compound of formula
124
with a heterocyclic compound of formula
BNH2IX
to give a compound of formula
125
wherein B is a 5-membered heterocycle of the formulae
126
and wherein G is a leaving group and the rermaining substituents have the significances given in claim 1, and if desired, converting a functional group in a compound of formula I into another functional group.
28. A compound of formula I
127
wherein
A1 and A2 are phenyl;
R1 is hydrogen or lower alkyl;
R2 and R2 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen and trifluoromethyl;
X signifies two hydrogen atoms not forming a bridge; and
B is a 5-membered heterocyclic group of formulae
128
wherein
R4 and R5 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, cyclohexyl, lower alkyl-cyclohexyl and trifluoromethyl, with the proviso that at least one of R4 or R5 has to be hydrogen; or a pharmaceutically acceptable salt thereof.
29. The compound of claim 28 of formula I wherein the compound is 2,2-Diphenyl-N-(5-propyl-1,3,4oxadiazol-2-yl)-acetamide.
30. The compound of claim 28 of formula I wherein the compound is N-1,3,4Oxadiazol-2-yl-2,2-diphenyl-acetamide.
31. The compound of claim 28 of formula I wherein the compound is N-(5-Ethyl-1,3,4oxadiazol-2-yl)-2,2-diphenyl-acetamide.
32. The compound of claim 28 of formula I wherein the compound is N-(5-Ethyl-1,3,4oxadiazol-2-yl)-2,2-diphenyl-acetamide.
33. The compound of claim 28 of formula I wherein the compound is N-(5-Cyclopropyl-1,3,4oxadiazol-2-yl)-2,2-diphenyl-acetamide.
34. The compound of claim 28 of formula I wherein the compound is N-(5-Cyclopropylmethyl-1,3,4oxadiazol-2-yl)-2,2-diphenyl-acetamide.
35. The compound of claim 28 of formula I wherein the compound is N-(5-Ethyl-oxazol-2-yl)-2,2-diphenyl-acetamide.
36. The compound of claim 28 of formula I wherein the compound is N-(5-Methyl-oxazol-2-yl)-2,2-diphenyl-acetamide.
37. The compound of claim 28 of formula I wherein the compound is N-(4-Methyl-oxazol-2-yl)-2,2-diphenyl-acetamide.
38. The compound of claim 28 of formula I wherein the compound is N-(3-Methyl-1,2,4oxadiazol-5-yl)-2,2-diphenyl-acetamide.
39. The compound of claim 28 of formula I wherein the compound is N-(3-cyclopropyl-1,2,4oxadiazol-5-yl)-2,2-diphenyl-acetamide.
40. The compound of claim 28 of formula I wherein the compound is N-(5-Methyl-1,2,4oxadiazol-3-yl)-2,2-diphenyl-acetamide.
41. The compound of claim 28 of formula I wherein the compound is N-(5-Methyl-1,3,4oxadiazol-2-yl)-2,2-diphenyl-acetamide.
42. The compound of claim 28 of formula 1 wherein the compound is N-5-(2-methoxy-ethyl)-1,3,4oxadiazol-2-yl-2,2-diphenyl-acetamide.
43. The compound of claim 28 of formula I wherein the compound is N-(5-trifluoromethyl-1,3,4oxadiazol-2-yl)-2,2-diphenyl-acetamide.
44. The compound of claim 28 of formula I wherein the compound is 2,2-Diphenyl-N-(5-propyl-oxazol-2-yl)-acetamide.
45. A compound of formula 1 N-(5-Ethyl-oxazol-2-yl)-2,2-diphenyl-acetamide.
46. A compound of formula 1 N-(5-Methyl-oxazol-2-yl)-2,2-diphenyl-acetamide.
47. A pharmaceutical composition comprising a therapeutically effective amount of the compound according of formula I
129
wherein
A1 and A2 are phenyl;
R1 is hydrogen or lower alkyl;
R2 and R2 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen and trifluoromethyl;
X signifies two hydrogen atoms not forming a bridge; and
B is a 5-membered heterocyclic group of formulae
130
wherein
R4 and R5 signifies hydrogen, lower alkyl, lower alkoxy, cyclohexyl, lower alkyl-cyclohexyl or trifluoromethyl, with the proviso that at least one of R4 or R5 has to be hydrogen;
or a pharmaceutically acceptable salt thereof and a pharmaceutically inert carrier.
48. A method of treating neurological disorders comprising administering an effective amount of a compound of the formula I to a person in need of such treatment
131
wherein
A1 and A2 are phenyl;
R2 and R2 are independently selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen and trifluoromethyl;
X signifies two hydrogen atoms not forming a bridge; and
B is a 5-membered heterocyclic group of formulae
132
wherein
R4 and R5 signifies hydrogen, lower alkyl, lower alkoxy, cyclohexyl, lower alkyl-cyclohexyl or trifluoromethyl, with the proviso that at least one of R4 or R5 has to be hydrogen, or a pharmaceutically acceptable salt thereof.