其它产品项目整合

项目整合的本质是一项集合成方法学、反应工程学与过程分析技术于一体的系统工程。其核心逻辑可以概括为以下几点：源头优选：利用如N-硝胺化学等底层方法学突破，从分子层面颠覆传统高成本、高污染路线。过程强化：依托连续流技术，攻克有机金属试剂应用、光化学反应放大等“不可能”任务，实现高危工艺的本质安全。系统集成：整合“反应-淬灭-分离”全流程，利用微流控与在线分析技术，消除批次间的差异，实现药品制造的连续化与智能化。当前，中间体工艺研发正在经历从“经验驱动”向“数据驱动”的转变。AI辅助路线设计、自动化高通量筛选与连续制造平台的结合，将使得“分子结构与最优工艺路径”之间的映射关系逐渐清晰。未来的竞争优势，将属于那些能够将底层化学创新与先进工程技术进行无缝整合的研发体系。
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其它产品项目整合

Ifosfamide CAS Registry Number: 3778-73-2 异环磷酰胺

CAS Name: N,3-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide
Additional Names: 3-(2-chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorin-2-oxide; ipho...
Literature References: Cytostatic agent, related structurally to cyclophosphamide, q.v. Prepn: FR 1530962 (1968 to Asta), C.A. 71, 49998m (1969); H. Arnold et al., US 3732340 (1973 to Asta). Chemical properties: H. Arnold, Proc. 5th Int. Congr. Chemother. Vienna (Verhandlungen, Vienna, 1967) 2, pp 751-754. Pharmacology: N. Brock, ibid. pp 155-161. Molecular structure and conformation: H. A. Brassfield et al., J. Am. Chem. Soc. 97, 4143 (1975). Mass spectrometry: M. Przybylski et al., Biomed. Mass Spectrom. 4, 209 (1977). Mechanism of action: S. Tomita et al., Chemotherapy (Tokyo) 25, 3014 (1977). Metabolism: A. Takamizawa et al., Chem. Pharm. Bull. 25, 2900 (1977); eidem, J. Med. Chem. 17, 1237 (1974). Toxicity studies: R. Marcy et al., IRCS Med. Sci. Libr. Compend. 5, 427, 478 (1977). Mutagenicity studies: D. Wald, J. Mutat. Res. 56, 319 (1978); G. R. Mohn, J. Ellenberger, ibid. 32, 331 (1976). Clinical studies: P. J. Creaven et al., Cancer Treat. Rep. 60, 445, 451 (1976); J. Schnitker et al., Arzneim.-Forsch. 26, 1793 (1976). Symposium on clinical efficacy and comparison with cyclophosphamide: Cancer Chemother. Pharmacol. 18, Suppl. 2, S1-S58 (1986). Reviews of pharmacology, toxic effects and clinical activity: M. Zalupski, L. H. Baker, J. Natl. Cancer Inst. 80, 556-566 (1988); S. E. Schoenike, W. J. Dana, Clin. Pharm. 9, 179-191 (1990).

Mitobronitol CAS Registry Number: 488-41-5 二溴甘露醇

CAS Name: 1,6-Dibromo-1,6-dideoxy-D-mannitol
Additional Names: 1,6-dideoxy-1,6-dibromo-D-mannitol; dibromomannitol; DBM
Trademarks: Myebrol (Kyorin); Myelobromol (Enzypharm)
Percent Compo...
Literature References: Cytostatic agent; the first dibromohexitol introduced into clinical use. Manuf: GB 959407 (1964 to Chinoin). Pharmaco-biochemical studies: J. Szabo et al., Neoplasma 20, 13 (1973). Clinical studies: D. F. Chiuten et al., Cancer 47, 442 (1981). Comparative study with busulfan, q.v.: R. T. Silver et al., Cancer 60, 1442 (1987).

Spirogermanium CAS Registry Number: 41992-23-8

CAS Name: 8,8-Diethyl-N,N-dimethyl-2-aza-8-germaspiro[4.5]decane-2-propanamine
Additional Names: 2-[3-(dimethylamino)propyl]-8,8-diethyl-2-aza-8-germaspiro[4.5]decane
Percent Composition: C ...
Literature References: Cytostatic germanium deriv. Prepn: L. M. Rice, DE 2243550; idem, US 3825546 (1973, 1974 both to Geschickter Fund for Med. Res.); L. M. Rice et al., J. Heterocycl. Chem. 11, 1041 (1974). Toxicology study: M. C. Henry et al., Preclinical Toxicologic Evaluation (PB-264117, 1977) 213 pp. Metabolism study: D. Garteiz et al., Drug Metab. Dispos. 19, 44 (1991). Clinical evaluation: P. S. Schein et al., Cancer Treat. Rep. 64, 1051 (1980); C. Tropie et al., ibid. 65, 119 (1981). Toxicity study: M. C. Henry et al., ibid. 64, 1207 (1980).

Resibufogenin CAS Registry Number: 465-39-4 酯蟾毒配基,蟾力苏

CAS Name: (3b,5b,15b)-14,15-Epoxy-3-hydroxy-5-bufa-20,22-dienolide
Trademarks: Respigon (Taisho)
Percent Composition: C 74.97%, H 8.39%, O 16.64%
Literature References: Cytotoxic constituent of toad venom. Isoln: Meyer, Helv. Chim. Acta 35, 2444 (1952); Linde, Meyer, Pharm. Acta Helv. 33, 327 (1958). Structure: Thiessen, Chem. Ind. (London) 1958, 440; Linde, Meyer, Experientia 14, 238 (1958); eidem, Helv. Chim. Acta 42, 807 (1959). Synthesis: Pettit et al., J. Org. Chem. 36, 3736 (1971); Haede et al., Ann. 1973, 5. Stereochemical study of cytotoxic properties: Y. Kamono et al., J. Chem. Res. Synop. 1977, 78. Pharmacology: Leigh, Caldwell, J. Pharm. Pharmacol. 21, 708 (1969).

Oleandrin CAS Registry Number: 465-16-7 欧夹竹桃苷

CAS Name: (3b,5b,16b)-16-(Acetyloxy)-3-[(2,6-dideoxy-3-O-methyl-a-L-arabino-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide
Additional Names: neriolin
Trademarks: Corrigen; Folinerin
Per...
Literature References: Cytotoxic glycoside from the leaves of Nerium oleander L., Apocynaceae (Laurier rose). Component of the commercial oleander extract, Anvirzel. Isoln: Tanret, Compt. Rend. 194, 914 (1932); Neumann, Ber. 70, 1547 (1937). Prepn by enzymic hydrolysis of urechitoxin: Hassall, J. Chem. Soc. 1951, 3193. Structure: Tschesche, Ber. 70, 1554 (1937); Krasso et al., Helv. Chim. Acta 46, 1691 (1963). LC/MS/MS determn in tissues and biological fluids: E. R. Tor et al., J. Agric. Food Chem. 53, 4322 (2005). Apoptotic activity study: Y. Sreenivasan et al., Biochem. Pharmacol. 66, 2223 (2003). Pharmacology: D. Ni et al., J. Exp. Ther. Oncol. 2, 278 (2002). Review of toxicity: S. D. Langford, P. J. Boor, Toxicology 109, 1-13 (1996).

Eleutherobin CAS Registry Number: 174545-76-7

CAS Name: [(4R,4aS,5Z,7R,10S,11S,12aR)-3,4,4a,7,10,11,12,12a-Octahydro-7-methoxy-1,10-dimethyl-4-(1-methylethyl)-11-[[(2E)-3-(1-methyl-1H-imidazol-4-yl)-1-oxo-2-propenyl]oxy]-7,10-epoxybenzocyclod...
Literature References: Cytotoxic glycosylated diterpene isolated from the marine soft coral, Eleutherobia sp. Enhances tubulin polymerization and stablization of microtubules similar to paclitaxel, q.v. Isoln and structure determn: W. H. Fenical et al., US 5473057 (1995 to Univ. Calif.). Induction of tubulin polymerization and mode of action: B. H. Long et al., Cancer Res. 58, 1111 (1998). Total synthesis: K. C. Nicolaou et al., J. Am. Chem. Soc. 120, 8674 (1998); X. T. Chen et al., ibid. 121, 6563 (1999). Solid-state and solution conformations: B. Cinel et al., Tetrahedron Lett. 41, 2811 (2000). Structure-activity: I. Ojima et al., Proc. Natl. Acad. Sci. USA 96, 4256 (1999). Brief review: T. Lindel, Angew. Chem. Int. Ed. 37, 774-776 (1998).

Pergolide CAS Registry Number: 66104-22-1 培高利特

CAS Name: (8b)-8-[(Methylthio)methyl]-6-propylergoline
Additional Names: D-6-n-propyl-8b-methylmercaptomethylergolinePercent Composition: C 72.56%, H 8.33%, N 8.91%, S 10.20%
Literature References: D1/D2 dopaminergic agonist that also decreases plasma prolactin concentrations. Prepn: E. C. Kornfeld, N. J. Bach, US 4166182 (1979 to Lilly). Industrial synthesis: W. Cabri et al., Org. Process Res. Dev. 10, 198 (2006). Dopaminergic effects in rats: R. W. Fuller et al., Life Sci. 24, 375 (1979); T. T. Yen et al., ibid. 25, 209 (1979). Clinical pharmacology: L. Lemberger, R. E. Crabtree, Science 205, 1151 (1979). Pharmacological evaluation as antiparkinson agent: W. C. Koller, Neuropharmacology 19, 831 (1980). Clinical study in galactorrhea: J. T. Callaghan et al., Life Sci. 28, 95 (1981); in hyperprolactinemia: S. Francks et al., Lancet 2, 659 (1981); in treatment of pituitary tumors secreting prolactin or growth hormone: D. L. Kleinberg et al., N. Engl. J. Med. 309, 704 (1983). Clinical studies in Parkinson's disease: J. Jankovic, J. Orman, Adv. Neurol. 45, 551 (1986); C. W. Olanow, M. J. Alberts, ibid. 555; in restless legs syndrome: C. Trenkwalder et al., Neurology 62, 1391 (2004). Comprehensive description: D. J. Sprankle, E. C. Jensen, Anal. Profiles Drug Subs. Excip. 21, 375-413 (1992). Review of clinical experience in Parkinson's disease: U. Bonuccelli et al., Clin. Neuropharmacol. 25, 1-10 (2002).

Chlorfenethol CAS Registry Number: 80-06-8 4,4'-二氯-α-甲基二苯基甲醇

CAS Name: 4-Chloro-a-(4-chlorophenyl)-a-methylbenzenemethanol
Additional Names: 4,4'-dichloro-a-methylbenzhydrol; p,p'-dichlorodiphenylmethyl carbinol; 1,1-bis(p-chlorophenyl)ethanol; 1,1-bis(p...
Literature References: DDT Structural analog. Prepn: Ruthruff et al., US 2430586 (1947 to Sherwin-Williams); GB 831421 (1960 to Metal Thermit). Activity: O. Grummitt, Science 111, 361 (1950).

Ganirelix CAS Registry Number: 124904-93-4 加尼瑞克

CAS Name: N-Acetyl-3-(2-naphthalenyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-seryl-L-tyrosyl-N6-[bis(ethylamino)methylene]-D-lysyl-L-leucyl-N6-[bis(ethylamino)methylene]-L-lys...
Literature References: Decapeptide LH-RH antagonist. Prepn and structure-activity studies: J. J. Nestor, Jr. et al. in Peptides 1988: Proc. 20th Eur. Peptide Symp., G. Jung, E. Bayer, Eds. (Walter de Gruyter, Berlin, 1989) pp 592-594; eidem, J. Med. Chem. 35, 3942 (1992). Improved synthesis: H. B. Arzeno et al., Int. J. Pept. Protein Res. 41, 342 (1993). Degradation in aq soln: R. G. Strickley et al., Pharm. Res. 7, 530 (1990). Clinical pharmacology and pharmacokinetics: J. Rabinovici et al., J. Clin. Endocrinol. Metab. 75, 1220 (1992). Clinical trial in assisted fertilization: P. Devroey et al., Hum. Reprod. 13, 3023 (1998).

Cetrorelix CAS Registry Number: 120287-85-6 西曲瑞克

CAS Name: N-Acetyl-3-(2-naphthalenyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-seryl-L-tyrosyl-N5-(aminocarbonyl)-D-ornithyl-L-leucyl-L-arginyl-L-prolyl-D-alaninamide
Additio...
Literature References: Decapeptide LH-RH antagonist. Prepn: A. V. Schally, S. Bajusz, EP 299402 (1989 to Asta); eidem, US 4800191 (1989); S. Bajusz et al., Int. J. Pept. Protein Res. 32, 425 (1988). Structural study: A. Müller et al., ibid. 43, 264 (1994). HPLC determn in plasma: H. H. Raffel et al., J. Chromatogr. B 653, 102 (1994). Pharmacology: T. Reissmann et al., Eur. J. Cancer 32A, 1574 (1996). Clinical evaluation in prostatic cancer: D. Gonzalez-Barcena et al., Urology 45, 275 (1995); in assisted fertilization: C. Albano et al., Fertil. Steril. 67, 917 (1997).