Candidate Drug 99/373 (Anti-osteoporotic)
    Compound 99/373 is antiresorptive agent useful for Osteoporosis accompanying menopause and other estrogen deficiency states.

  • Compound has no/negligible estrogenic profile (Uterotrophic side effect) on genital tract tissue.

  • Compound has low thrombogenic activity in comparison to known drug (Raloxifene)

  • Completed preclinical studies and Permission for conducting phase I Clinical trial has been obtained from DCGI

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  • Background:
  • Osteoporosis, which has been defined as a “state of low bone mass” is one of the major aging problems of the society. Osteoporosis is a metabolic disorder characterized by microarchitectural deterioration of bone tissue leading to enhanced bone fragility and consequent increase in fracture risk in older members of the population. Osteoporosis fractures occur most commonly in the spine, hip, distal radius and ribs. The risk is high in women as compared to men and increases sharply after 50 years of age. Factors predisposing towards osteoporosis include family history, genetic factors, hormonal factors, inadequate nutrition, and intake of certain medications, immobility and disease. The quality of life is greatly impaired in persons with sever osteoporosis. It is known to affect >50% of women and 30% men over the age of 50 years. In women, there is also an accelerated rate of bone loss immediately and for variable number of years following menopause.

  • Most of the pharmacological agents available for clinical use such as calcium, vitamin D and its analogue, calcitonin, bisphosphonates, raloxifene, hormone replacement therapy (HRT) etc. act by decreasing the rate of bone resorption, thereby slowing the rate of bone loss. Timely administration of such antiresorptive agents prevents bone loss.

  • The only side effect of calcium therapy is development of renal stones. The major disadvantage in calcitonin use is its high cost. Tachyphylaxis can develop in some individuals under calcitonin treatment. Bisphosphonates are poorly absorbed and may cause gastrointestinal irritation, diarrhea and constipation. Raloxifene has been reported to increase incidence of hot flashes, deep vein thrombosis, pulmonary embolism and leg cramps. 

  • Hormone replacement therapy, though effective in preventing bone loss following ovariectomy or menopause in women, is associated with increased risk of endometrial hyperplasia and carcinoma, breast cancer, and thromboembolic diseases. Parathyroid hormone [PTH(1–34)], the sole clinically used anabolic agent, has been recommended recently by the US Food and Drug Administration to carry a black box warning because it is associated with an increased risk of osteosarcoma in rats. Intermittently administered PTH (iPTH) not only increases bone mass but also improves bone quality and strength by positive effects on the microarchitecture and geometry of bone..

  • In India the estimated number of fracture related cases range in the order of 50 million per year. A course of daily oral treatment for fracture healing is expected to last for 90 to 120 days per patient per incident. In the fracture healing incidence alone, 50 billion or 5000 crores of formulary dosages will be utilized annually. Bone anabolic therapy is also expected to impact secondary osteoporosis as well as primary osteoporosis. The prevalence of osteoporosis in India alone is estimated at 300 million cases. The market potential of an affordable bone anabolic therapy in India is enormous. If this treatment were to be taken onto the global stage, the market potential is limitless. Currently, there is no oral therapy available. 

    Unique Features CDRI Comp 99/373
  • CDRI Compound 99/373 is a promising alternative option in the prevention and treatment of osteoporosis. It 99/373 is an orally active and achiral compounds,which has excellent antiresorptive activity, backed by elegant bone biology studies. It has favourable animal PK profile. Found safe in preclinical regulatory pharmacology and toxicity studies. CDRI has obtained DCGI permission to carry out Phase-I clinical trial. National and international patents granted which are active. Product has advantage over existing clinically used drugs like raloxifene and bisphoaphonates in terms of its efficacy as well as toxicity. Cost effective due to “one pot synthesis”
  • Patent Status:
    APPLICATION NUMBER FILING DATE PATENT NUMBER DATE OF GRANT TITLE INVENTOR(S)
    0246DEL2004 20-Feb-04 237915 12-Jan-10 Novel mercapto phenyl naphthyl methane derivatives and preparation thereof Sangita, Atul Kumar, Man Mohan Singh, Girish Kumar Jain, Puvvada Sri Ramchandra Murthy & Suprabhat Ray
    CA-2524568 02-Nov-05 2524568 17-Jul-12 Substituted mercapto phenyl naphthyl methane derivatives as SERM for the prevention and treatment of esteoporosis and other estrogen dependent disorders and as contraceptives
    CN-ZL200380110327.4 29-Nov-05 200380110327 16-Dec-09
    EP-20030780487 17-Nov-05 1692101 06-Jul-11
    FR-20030780487 17-Nov-05 1692101 06-Jul-11
    Gb-20030780487 17-Nov-05 1692101 06-Jul-11
    US-11/812251 15-Jun-07 7582653 01-Sep-09 Novel mercaptophenyl naphthyl methane compounds and synthesis thereof
    US-10/809845 26-Mar-04 7250446 31-Jul-07 Substituted mercapto phenyl naphthyl methane derivatives as SERM for the prevention and treatment of esteoporosis and other estrogen dependent disorders and as contraceptives
    PCT/IB03/006247 23-Dec-03     Mercapto-phenyl-naphthyl-methane derivatives and preparation thereof