149606-27-9

Usage

Uses

Used in Pharmaceutical Industry:
(2S)-2-[[(2S)-2-dimethylamino-3-methyl-butanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(3R)-3-[(1R,2R)-1-methoxy-2-(phenethylcarbamoyl)propyl]pyrrolidin-1-yl]-5-methyl-1-oxo-heptan-4-yl]-N,3-dimethyl-butanamide is used as a potential therapeutic agent for its ability to interact with biological targets due to its structural complexity and multiple functional groups.
Used in Diagnostic Applications:
In the field of diagnostics, (2S)-2-[[(2S)-2-dimethylamino-3-methyl-butanoyl]amino]-N-[(3R,4S,5S)-3 -methoxy-1-[(3R)-3-[(1R,2R)-1-methoxy-2-(phenethylcarbamoyl)propyl]pyr rolidin-1-yl]-5-methyl-1-oxo-heptan-4-yl]-N,3-dimethyl-butanamide may be utilized for the development of assays or imaging agents, capitalizing on its capacity to bind to specific biological molecules or structures, which could be indicative of certain diseases or conditions.
Used in Drug Delivery Systems:
(2S)-2-[[(2S)-2-dimethylamino-3-methyl-butanoyl]amino]-N-[(3R,4S,5S)-3 -methoxy-1-[(3R)-3-[(1R,2R)-1-methoxy-2-(phenethylcarbamoyl)propyl]pyr rolidin-1-yl]-5-methyl-1-oxo-heptan-4-yl]-N,3-dimethyl-butanamide's structural features may also lend itself to the design of drug delivery systems, where it could serve as a carrier or component in targeted drug delivery platforms, enhancing the bioavailability and efficacy of associated therapeutic agents.

InChI:InChI=1/C39H67N5O6/c1-13-27(6)35(43(10)39(48)33(25(2)3)41-38(47)34(26(4)5)42(8)9)31(49-11)24-32(45)44-23-17-20-30(44)36(50-12)28(7)37(46)40-22-21-29-18-15-14-16-19-29/h14-16,18-19,25-28,30-31,33-36H,13,17,20-24H2,1-12H3,(H,40,46)(H,41,47)/t27-,28+,30-,31+,33-,34-,35+,36+/m0/s1

Synthetic route

phenethylamine (64-04-0) + Dov-Val-Dil-Dap (163768-53-4) → TZT-1027 (149606-27-9)

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In N,N-dimethyl-formamide Yield given;
With triethylamine; diethyl cyano phosphate In DMF (N,N-dimethyl-formamide)

(3R,4S,5S)-4--3-methoxy-5-methylheptanoic acid (135383-56-1) → TZT-1027 (149606-27-9)

Conditions

Yield

Multi-step reaction with 9 steps 1: H2SO4 / CH2Cl2 2: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 3: 1,3-dicyclohexylcarbodiimide / CH2Cl2 4: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 5: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 6: trifluoroacetic acid / CH2Cl2 / 1 h / Ambient temperature 7: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 8: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 9: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

tert-Butyl (3R,4S,5S)-3-methoxy-4--5-methylheptanoate (120205-58-5) → TZT-1027 (149606-27-9)

Conditions

Yield

Multi-step reaction with 8 steps 1: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 2: 1,3-dicyclohexylcarbodiimide / CH2Cl2 3: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 4: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 5: trifluoroacetic acid / CH2Cl2 / 1 h / Ambient temperature 6: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 7: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 8: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

tert-Butyl (3R,4S,5S)-3-methoxy-4-(N-methylamino)-5-methylheptanoate (474645-22-2) → TZT-1027 (149606-27-9)

Conditions

Yield

Multi-step reaction with 7 steps 1: 1,3-dicyclohexylcarbodiimide / CH2Cl2 2: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 3: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 4: trifluoroacetic acid / CH2Cl2 / 1 h / Ambient temperature 5: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 6: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 7: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

(3R,4S,5S)-tert-butyl 4-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate (120205-53-0) → TZT-1027 (149606-27-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: trifluoroacetic acid / CH2Cl2 / 1 h / Ambient temperature 2: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 3: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 4: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

tert-butyl (3R,4S,5S)-4-[(2S)-2-[[(benzyloxy)carbonyl]amino]-N,3-dimethylbutanamido]-3-methoxy-5-methylheptanoate (120205-52-9) → TZT-1027 (149606-27-9)

Conditions

Yield

Multi-step reaction with 6 steps 1: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 2: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 3: trifluoroacetic acid / CH2Cl2 / 1 h / Ambient temperature 4: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 5: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 6: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

Dov-Val-Dil-Dap-OBzl (163768-52-3) → TZT-1027 (149606-27-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 2: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

(3R,4S,5S)-4-[(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-N,3-dimethylbutanamido]-3-methoxy-5-methylheptanoate (177423-00-6) → TZT-1027 (149606-27-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 2: trifluoroacetic acid / CH2Cl2 / 1 h / Ambient temperature 3: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 4: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 5: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

(3R,4S,5S)-4-(Benzyloxycarbonyl-methyl-amino)-3-methoxy-5-methyl-heptanoic acid methyl ester (149664-79-9) → TZT-1027 (149606-27-9)

Conditions

Yield

Multi-step reaction with 10 steps 1: 1N aq. NaOH / dioxane / 3 h / Ambient temperature 2: H2SO4 / CH2Cl2 3: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 4: 1,3-dicyclohexylcarbodiimide / CH2Cl2 5: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 6: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 7: trifluoroacetic acid / CH2Cl2 / 1 h / Ambient temperature 8: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 9: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 10: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

(3R,4S,5S)-4-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoic acid (133120-89-5) → TZT-1027 (149606-27-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: diethyl phosphorocyanidate, Et3N / dimethylformamide / a) 0 deg C, 2 h, b) RT, 16 h 2: H2 / 5percent Pd/C / 2-methyl-propan-2-ol; H2O / 2 h 3: diethyl phosphorocyanidate, Et3N / dimethylformamide View Scheme

3-methoxy-2-methyl-N-phenethyl-3-pyrrolidin-2-yl-propionamide + (3R,4S,5S)-4-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoic acid (133120-89-5) → TZT-1027 (149606-27-9)

Conditions	Yield
With triethylamine; diethyl cyano phosphate In DMF (N,N-dimethyl-formamide)

Upstream product

• 135383-56-1 (3R,4S,5S)-4--3-methoxy-5-methylheptanoic acid 
• 120205-58-5 tert-Butyl (3R,4S,5S)-3-methoxy-4--5-methylheptanoate 
• 133120-89-5 (3R,4S,5S)-4-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoic acid 
• 149664-79-9 (3R,4S,5S)-4-(Benzyloxycarbonyl-methyl-amino)-3-methoxy-5-methyl-heptanoic acid methyl ester 
• 177423-00-6 (3R,4S,5S)-4-[(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-N,3-dimethylbutanamido]-3-methoxy-5-methylheptanoate 
• 163768-52-3 Dov-Val-Dil-Dap-OBzl 
• 120205-52-9 tert-butyl (3R,4S,5S)-4-[(2S)-2-[[(benzyloxy)carbonyl]amino]-N,3-dimethylbutanamido]-3-methoxy-5-methylheptanoate 
• 120205-53-0 (3R,4S,5S)-tert-butyl 4-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate 
• 474645-22-2 tert-Butyl (3R,4S,5S)-3-methoxy-4-(N-methylamino)-5-methylheptanoate 
• 64-04-0 phenethylamine 
• 163768-53-4 Dov-Val-Dil-Dap 

Relevant academic research and scientific papers

TETRAPEPTIDE DERIVATIVE CRYSTALS

The invention provides crystals of N2-(N,N-dimethyl-L-valyl)-N-[(1S,2R)-2-methoxy-4-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[(2-phenylethyl)amino]propyl]-2-pyrrolidinyl]-1-[(S)-1-methylpropyl ]- 4-oxobutyl]-N-methyl-L-valinamide or salts thereof which possess potent antitumor activity and methods for their preparation.

Synthesis and antitumor activity of novel dolastatin 10 analogs

Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.