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

Temozolomide CAS Registry Number: 85622-93-1 替莫唑胺

CAS Name: 3,4-Dihydro-3-methyl-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide
Additional Names: 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one; methazolastoneTrademarks: Tem...
Literature References: Imidazotetrazine alkylating agent. Prepn: E. Lunt et al., DE 3231255 (1983 to May Baker); eidem, US 5260921 (1993 to Cancer Res. Campaign Technol.); M. F. G. Stevens et al., J. Med. Chem. 27, 196 (1984). Crystal structure and structure-activity study: P. R. Lowe et al., ibid. 35, 3377 (1992). Synthesis: Y. Wang et al., J. Org. Chem. 62, 7288 (1997). HPLC determn in plasma and urine: F. Shen et al., J. Chromatogr. B 667, 291 (1995). Review of pharmacology and clinical efficacy in melanoma and brain tumor: E. S. Newlands et al., Cancer Treat. Rev. 23, 35-61 (1997); S. J. Danson, M. R. Middleton, Expert Rev. Anticancer Ther. 1, 13-19 (2001).

Disofenin CAS Registry Number: 65717-97-7 地索苯宁

CAS Name: N-[2-[[2,6-Bis(1-methylethyl)phenyl]amino]2-oxoethyl]-N-(carboxymethyl)glycine
Additional Names: [[[(2,6-diisopropylphenyl)carbamoyl]methyl]imino]diacetic acid; (2,6-diisopropylacetan...
Literature References: Iminodiacetic acid analog. Prepn of acid and 99mTc-complex: M. de Schrijver, DE 2723605; idem, US 4316883 (1977, 1982 both to Solco Basel). High yield synthesis of acid: M. P. Best et al., Aust. J. Chem. 35, 2371 (1982). Biodistribution: G. Subramanian et al., Nuklearmedizin Suppl. 16, 136 (1978). Chromatographic determn of radiochemical purity: A. M. Zimmer et al., Eur. J. Nucl. Med. 7, 88 (1982). Chemical and biological properties: B. Zmbova et al., Appl. Radiat. Isot. 38, 35 (1987). Pharmacokinetics: I. A. Fraser et al., Eur. J. Nucl. Med. 14, 431 (1988); J. E. Love et al., ibid. 436. Clinical evaluation as hepatobiliary imaging agent: R. C. Stadalnik et al., Radiology 140, 797 (1981).

Lidofenin CAS Registry Number: 59160-29-1 N-(2,6-二甲基苯基氨基甲酰甲基)亚氨基二乙酸

CAS Name: N-(Carboxymethyl)-N-[2-[(2,6-dimethylphenyl)amino]-2-oxoethyl]glycine
Additional Names: N-(2,6-dimethylacetanilide)iminodiacetic acid; N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacet...
Literature References: Iminodiacetic acid analog. Prepn of compd and 99mTc-complex: M. D. Loberg et al., BE 840556; eidem, US 4017596 (1976, 1977 both to Research Corp.); and imaging studies: M. D. Loberg et al., J. Nucl. Med. 17, 633 (1976). Structural studies: M. D. Loberg, A. T. Fields, Int. J. Appl. Radiat. Isot. 29, 167 (1978). Chromatographic determn of radiochemical purity: A. M. Zimmer et al., Eur. J. Nucl. Med. 7, 88 (1982). Biodistribution and clinical kinetics: J. Ryan et al., J. Nucl. Med. 18, 995 (1977). Clinical studies of diagnostic use as hepatobiliary imaging agent: H. S. Weissmann et al., Am. J. Roentgenol. 132, 523 (1979); R. W. Nicholson et al., Br. J. Radiol. 53, 878 (1980).

Imiquimod CAS Registry Number: 99011-02-6 咪喹莫特

CAS Name: 1-(2-Methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine
Additional Names: 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinolineTrademarks: Aldara (3M Pharma)
Percent Composition: C 69.97%, H ...
Literature References: Immune response modifier; stimulates production of interferon-a, q.v. Prepn: J. F. Gerster, EP 145340; idem, US 4689338 (1985, 1987 both to Riker). Mechanism of action study: K. Megyeri et al., Mol. Cell. Biol. 15, 2207 (1995). Clinical pharmacology: P. L. Witt et al., Cancer Res. 53, 5176 (1993). Clinical trial for genital warts: L. Edwards et al., Arch. Dermatol. 134, 25 (1998). Series of articles on pharmacology and clinical experience in cutaneous viral infections: J. Am. Acad. Dermatol. 43, S1-S30 (2000).

Resiquimod CAS Registry Number: 144875-48-9 雷西莫特

CAS Name: 4-Amino-2-(ethoxymethyl)-a,a-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanolPercent Composition: C 64.95%, H 7.05%, N 17.82%, O 10.18%
Literature References: Immune response modulator structurally similar to imiquimod, q.v. Induces cytokine secretion by monocytes and activates antibody secretion by B cells. Prepn: J. F. Gerster et al., WO 9215582; eidem, US 5389640 (1992, 1995 both to 3M). Immunomodulating and antiviral activities: M. A. Tomai et al., Antiviral Res. 28, 253 (1995). Mechanism of action study: G. A. Bishop et al., Cell. Immunol. 208, 9 (2001). Clinical evaluation in genital herpes: S. L. Spruance et al., J. Infect. Dis. 184, 196 (2001). Review of development: J. J. Wu et al., Antiviral Res. 64, 79-83 (2004).

Gemtuzumab Ozogamicin CAS Registry Number: 220578-59-6 吉妥珠单抗奥唑米星

Trademarks: Mylotarg (Wyeth)
Literature References: Immunoconjugate of N-acetyl-g-calicheamicin with the humanized mouse monoclonal IgG4 k antibody, hP67.6, directed against the human CD33 antigen located on the surface of normal and leukemic myeloid cells, but not on normal hematopoietic stem cells. Designed to deliver antibody-targeted chemotherapy for treatment of acute myelocytic leukemia (AML). Prepn of conjugate: P. R. Hamann et al., EP 689845; eidem, US 5773001 (1996, 1998 both to Am. Cyanamid). In vitro antineoplastic activity: K. Naito et al., Leukemia 14, 1436 (2000). Clinical evaluation in AML: E. L. Sievers et al., Blood 93, 3678 (1999). Reviews of development and therapeutic potential: I. D. Bernstein, Leukemia 14, 474-475 (2000); I. Niculescu-Duvaz, Curr. Opin. Mol. Ther. 2, 691-696 (2000); of clinical experience: F. J. Giles, Expert Rev. Anticancer Ther. 2, 630-640 (2002).

Fingolimod CAS Registry Number: 162359-55-9 芬戈莫德

CAS Name: 2-Amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol
Percent Composition: C 74.22%, H 10.82%, N 4.56%, O 10.41%
Literature References: Immunomodulator evoking a reversible redistribution of lymphocytes from the circulation to secondary lymphatic tissue; synthetic analog of myriocin (ISP-1), a fungal metabolite used in traditional Chinese herbal medicine. Prepn: T. Fujita et al., WO 9408943; eidem, US 5604229 (1994, 1997 both to Yoshitomi); K. Adachi et al., Bioorg. Med. Chem. Lett. 5, 853 (1995); M. Kiuchi et al., J. Med. Chem. 43, 2946 (2000). Efficient synthesis: P. Durand et al., Synthesis 2000, 505. Clinical pharmacokinetics: B. D. Kahan et al., Transplantation 76, 1079 (2003). Clinical evaluation in renal transplant: H. Tedesco-Silva et al., ibid. 77, 1826 (2004). Review of immunopharmacology: P. Troncoso, B. D. Kahan, Clin. Biochem. 31, 369-373 (1998); of mechanism of action: V. Brinkmann, K. R. Lynch, Curr. Opin. Immunol. 14, 569-575 (2002); and pharmacology: T. T. Aki, B. D. Kahan, Exp. Opin. Biol. Ther. 3, 665-681 (2003); of development and therapeutic potential: F. J. Dumont, IDrugs 8, 236-253 (2005).

Actarit CAS Registry Number: 18699-02-0 阿克他利

CAS Name: 4-(Acetylamino)benzeneacetic acid
Additional Names: (p-acetamidophenyl)acetic acidTrademarks: Mover (Mitsubishi Kasei); Orcl (Nippon Shinyaku)
Percent Composition: C 62.17%, H 5.74...
Literature References: Immunomodulator. Prepn: S. Gabriel, Ber. 15, 834 (1882). See also: H. Munakata et al., DE 3317107; eidem, US 4720506 (1983, 1988 both to Mitsubishi Chem. Ind. and Nippon Shinyaku). Pharmacology: H. Fujisawa et al., Arzneim.-Forsch. 40, 693 (1990). Pharmacokinetics: K. Sugihara et al., ibid. 800, 806. Antiarthritic effect in mice: H. Fujisawa et al., ibid. 44, 64 (1994). Acute toxicity: K. Toshida et al., Oyo Yakuri 40, 117 (1990), C.A. 114, 17276q (1991).

Inosine Pranobex CAS Registry Number: 36703-88-5 异丙肌苷

CAS Name: Inosine mono[4-(acetylamino)benzoate] (salt) compd with 1-(dimethylamino)-2-propanol (1:3)
Additional Names: inosine:dimethylaminoisopropanol acetamidobenzoate (1:3); inosiplex; methi...
Literature References: Immunostimulant complex formed from the p-acetamidobenzoate salt of dimethylaminoisopropanol and inosine in a 3:1 molar ratio. Prepn: P. Gordon, DE 1965431; idem, US 3646007 (1971, 1972 both to Newport Pharm.). Antiviral activity: E. R. Brown, P. Gordon, Can. J. Microbiol. 18, 1463 (1972); R. L. Muldoon et al., Antimicrob. Agents Chemother. 2, 224 (1972). Stimulatory effect on T-cell function: L. Binderup, Int. J. Immunopharmacol. 7, 93 (1985). Pharmacology and therapeutic potential: D. M. Campoli-Richards et al., Drugs 32, 383 (1986). Clinical immunopharmacology: A. J. Glasky, J. F. Gordon, Cancer Detect. Prev. Suppl. 1, 597 (1987). Clinical trial in subacute sclerosing panencephalitis (SSPE): C. E. Jones et al., Lancet 1, 1034 (1982); G. Gascon et al., Brain Dev. 15, 346 (1993). Clinical trial in pre-AIDS patients: C. Pedersen et al., N. Engl. J. Med. 322, 1757 (1990). Review of efficacy in HIV infection: C. De Simone et al., Int. J. Immunopharmacol. 13, Suppl. 1, 19-27 (1991).

Sizofiran CAS Registry Number: 9050-67-3 裂裥菌素

Additional Names: Schizophyllan; SPG
Trademarks: Sonifilan (Kaken)
Literature References: Immunostimulant polysaccharide produced by the fungus Schizophyllum commune Fries. Polymer of repeating tetrasaccharide units composed of three b-(1®3)-linked D-glucopyranose residues, to one of which is attached a single b-(1®6)-linked D-glucopyranosyl side chain. Forms triple-stranded helix of mol wt ~450,000 in neutral aqueous solution. Prepn by fermentation: S. Kikumoto et al., JP 67 12000 (1967 to Taito), C.A. 67, 107386r (1967). Synthesis of the 3 possible tetrasaccharide units: K. Takeo, S. Tei, Carbohydr. Res. 145, 293 (1986). Host-mediated antitumor activity: N. Komatsu et al., Gann 60, 137 (1969). Pharmacology, toxicology and antitumor activity in mice: T. Matsuo et al., Arzneim.-Forsch. 32, 647 (1982). Macrophage stimulant activity in vitro: I. Sugawara et al., Cancer Immunol. Immunother. 16, 137 (1984). Clinical trial in cervical cancer: K. Okamura et al., Cancer 58, 865 (1986).