Claims
- 1. A method for enhancing a neurotrophin-induced activity of a neurotrophin responsive cell, said method comprising contacting said cell with a K-252a derivative of the formula: ##STR11## wherein: a) Z.sup.1 and Z.sup.2 together represent O; each R.sup.1, R.sup.2, R.sup.5, and R.sup.6 independently is H, F, Cl, Br, I, NO.sub.2, CN, alkyl of 1-6 carbons or NR.sup.13 R.sup.14 independently is H or n-alkyl of 1-6 carbons;
- Y is H, OH, NH.sub.2, n-alkyl of 1-6 carbons, CHO, OCONH.sub.2 benzyl,
- O-n-alkyl of 1-6 carbons, (CH.sub.2).sub.n OH or (CH.sub.2).sub.n NH.sub.2 where n is an integer of 1-6; then either
- 1) R is OH, OCONH.sub.2, or O-n-alkyl of 1-6 carbons; and
- X is CH.sub.2 OH, CH.sub.2 NH.sub.2, (or an acid salt thereof;) CH.sub.2 O-n-alkyl of 2-7 carbons CO.sub.2 R.sup.7 where R.sup.7 is H or alkyl of 1-6 carbons, CONHOR.sup.8, CONH(CH.sub.2).sub.n OR.sup.8 where n is an integer of 1-6 and R.sup.8 is H or an acyl derivative group, or CONHR.sup.9 where R.sup.9 is alkyl of 1-3 carbons; or
- 2) R and X are combined to form a linking group of the formula --CH.sub.2 OCR.sup.10 R.sup.11 O-- where each R.sup.10 and R.sup.11 independently is H or alkyl of 1-3 carbons; or --CH.sub.2 NR.sup.12 CO.sub.2 -- where R.sup.12 is H or alkyl of 1-3 carbons;
- or
- b) Z.sup.1 is H and Z.sup.2 is OH;
- Y is H or CHO;
- R is OH; and
- X is CONH(CH.sub.2).sub.2 OH, CO.sub.2 CH.sub.3, or CH.sub.2 OH; and
- R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are as defined in a);
- or
- c) Z.sup.1 and Z.sup.2 are both H and R, Y and X are as defined in b), except that X cannot be CO.sub.2 CH.sub.3 ; and when R.sup.1 is Br, X cannot be CH.sub.2 OH; and R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are as defined in a);
- or
- d) Z.sup.1 is H and Z.sup.2 is SR.sup.15 where R.sup.15 is n-alkyl of 1-3 carbons; and Y, R and X are defined as in b), except that when R.sup.15 is C.sub.2 H.sub.5, X cannot be CH.sub.2 OH; and R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are as defined in a).
- 2. A method for enhancing a neurotrophin-induced activity of a neurotrophin responsive cell, said method comprising contacting said cell with a K-252a derivative of the formula: ##STR12## wherein: a) when Z.sup.1 and Z.sup.2 together represent O, then either
- 1) each R.sup.1, R.sup.2, R.sup.5, and R.sup.6 independently is H, F, Cl, Br, I, NO.sub.2, CN, alkyl of 1-6 carbons, or NR.sup.13 R.sup.14 where each R.sup.13 and R.sup.14, independently, is H or n-alkyl of 1-6 carbons; and
- Y is H, OH, NH.sub.2, n-alkyl of 1-6 carbons, CHO, benzyl, O-n-alkyl of 1-6 carbons, (CH.sub.2).sub.n OH or (CH.sub.2).sub.n NH.sub.2 where n is an integer of 1-6; and each R.sup.3 and R.sup.4 independently is H or (CH.sub.2).sub.n CH(OH)CH.sub.2 OH, where n is an integer of 1-6;
- or
- 2) each R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 independently is H; and Y is as defined in a) 1), except that Y cannot be benzyl;
- or
- b) Z.sup.1 is H and Z.sup.2 is H, OH, or SR.sup.15, where R.sup.15 is n-alkyl of 1-3 carbons;
- Y is H or CHO; and
- each R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 is H.
- 3. A method for enhancing a neurotrophin-induced activity of a neurotrophin responsive cell, said method comprising contacting said cell with a K-252a derivative of the formula: ##STR13## wherein: a) each P1 and P2 is H or P1 and P2 together represent O; and each W1 and W2 is H or W1 and W2 together represent O; provided that each P1 and P2 is different from W1 and W2.
- 4. The method of claim 1, further comprising contacting said cell with an exogenous neurotrophin.
- 5. The method of claim 4, wherein said neurotrophin is NT-3.
- 6. The method of claim 2 further comprising contacting said cell with an exogenous neurotrophin.
- 7. The method of claim 6, wherein said neurotrophin is NT-3.
- 8. The method of claim 3 further comprising contacting said cell with an exogenous neurotrophin.
- 9. The method of claim 8 wherein said neurotrophin is NT-3.
Parent Case Info
This application is a continuation-in-part of U.S. Ser. No. 08/122,893, filed Sep.16, 1993, now U.S. Pat. No. 5,468,872.
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Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
122893 |
Sep 1993 |
|